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K Richards

Publications and source records attributed to K Richards.

At least 19 recordsLinked to original sources
PubMed2005

Subcellular localization of the Triple Gene Block movement proteins of Beet necrotic yellow vein virus by electron microscopy.

The Triple Gene Block proteins TGBp1, TGBp2, and TGBp3 of Beet necrotic yellow vein virus (BNYVV) are required for efficient cell-to-cell spread of the infection. The TGB proteins can drive cell-to-cell movement of BNYVV in trans when expressed from a co-inoculated BNYVV RNA 3-based 'replicon'. TGBp2 and TGBp3 expressed from the replicon were nonfunctional in this assay if they were fused to the green fluorescent protein (GFP), but addition of a hemagglutinin (HA) tag to their C-termini did not incapacitate movement. Immunogold labeling of ultrathin sections treated with HA-specific antibodies localized TGBp2-HA and TGBp3-HA to what are probably structurally modified plasmodesmata (Pd) in infected cells. A similar subcellular localization was observed for TGBp1. Large gold-decorated membrane-rich bodies containing what appear to be short fragments of endoplasmic reticulum were observed near the cell periphery. The modified gold-decorated Pd and the membrane-rich bodies were not observed when the TGB proteins were produced individually in infections using the Tobacco mosaic virus P30 protein to drive cell-to-cell movement, indicating that these modifications are specific for TGB-mediated movement.

Beta vulgaris↗
PubMed2005

Nonregulated expression of TGBp3 of hordei-like viruses but not of potex-like viruses inhibits beet necrotic yellow vein virus cell-to-cell movement.

Plant viruses containing a Triple Gene Block (TGB) movement protein gene cassette fall into two classes. We have shown previously that the third TGB protein (TGBp3) of beet necrotic yellow vein virus (BNYVV; Class 1) and peanut clump virus (Class 1) inhibit BNYVV intercellular movement when expressed from a co-inoculated BNYVV RNA 3-based replicon. Here we show that autonomous expression of TGBp3's of four other Class 1 viruses of various genera also inhibits BNYVV movement. No such effect was observed for four Class 2 virus TGBp3's, suggesting that the roles of Class 1 and 2 TGBp3's in movement differ significantly.

Genes, Viral↗
PubMed2005

A phase II study of dexamethasone, ifosfamide, cisplatin and etoposide (DICE) as salvage chemotherapy for patients with relapsed and refractory lymphoma.

The 4-day combination of dexamethasone, ifosfamide, cisplatin, and etoposide (DICE) is a salvage regimen for lymphoma. We report a prospective phase II multi-center trial of a modified DICE regimen in relapsed or refractory Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), constituting a single day of intravenous administration followed by 3 days of oral administration, aimed at reducing inpatient days without losing efficacy. Forty patients (median age 56, range 25 - 79) were included: 28 (70%) NHL, 9 (23%) HL and 3 (8%) CLL. Fifty-three per cent had received 2 prior treatment regimens. International Prognostic Index (IPI) was 2 in 75% of NHL patients. Patients aged 55 and those with previous autologous stem cell transplantation (ASCT) started on a lower-dose regimen, with dose escalation possible in 2 patients. Overall response rate was 41%. Thirty-eight per cent of patients had stable disease. With a median of 3.1 years of follow-up, estimated progression-free survival (PFS) and overall survival (OS) rates at 3 years were 15% and 43% respectively. OS was longer in the < 55 compared to the 55 age cohort (P = 0.0091), longer for HL than NHL (P = 0.59 and 0.039 respectively) and longer for Low/Low-Int IPI than High/High-Int IPI (P = 0.0074 and 0.0009 respectively). Median duration of inpatient stay was 3 days. There were no treatment-related deaths. In conclusion, this modification of DICE is an effective and well tolerated salvage regimen, even in this poor prognosis group of patients. Further clinical studies of DICE in first relapse and in older patients, possibly with the addition of rituximab, are warranted.

Adult↗
PubMed2004

Rapid screening for depression--validation of the Brief Case-Find for Depression (BCD) in medical oncology and palliative care patients.

Depression in oncology patients is under-recognised and associated with poor outcomes. Screening can increase case recognition. The Brief Case-Find for Depression (BCD) is a four-question, interviewer-administered instrument that has been previously validated in a general medical setting. The primary aim of this study was to validate the BCD in a medical oncology/palliative care setting, primarily by comparing its association with physical illness measures and with the Primary Care Evaluation of Mental Disorders (PRIME-MD), the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Eligible adult oncology patients gave informed consent and completed the above measures and a pain scale. Agreement between the BCD and other instruments was assessed. Construct validity was determined by comparing depressed/nondepressed patients with respect to performance status, symptoms, pain score and functional impairment. A total of 100 patients had a median age of 58 (range 21-90) and ECOG performance status (PS) 2 (0-4). In all, 60% had metastatic disease. The therapeutic goal was curative/adjuvant in 39% and palliative in 61%. Prevalence of depression according to the various measures was: BCD 34%, PRIME-MD 12%, BDI 19% and HADS 14%. In total, 45% of patients responded positively to a single-item screening question. The BCD showed fair agreement with the PRIME-MD (kappa=0.21), moderate agreement with the BDI (kappa=0.43) and fair agreement with the HADS (kappa=0.27). Against the PRIME-MD diagnosis of depression, the BCD had greater sensitivity, but lesser specificity and overall agreement, compared with the BDI and depression scale of the HADS. Patients with probable depression (according to BCD) had inferior PS (P=0.0064), increased pain (P=0.045) and greater impairment of functioning (PRIME-MD: P=0.0003). There was no association with gender, age, disease status or therapeutic goal. Depression is common in oncology patients. The BCD is a quick, easy-to-administer screen for depression, which has reasonable psychometric properties in this population.

Adult↗
PubMed2004

Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema.

BACKGROUND: Continuous positive airways pressure (CPAP) and bilevel non-invasive ventilation may have beneficial effects in the treatment of patients with acute cardiogenic pulmonary oedema. The efficacy of both treatments was assessed in the UK emergency department setting, in a randomised comparison with standard oxygen therapy. METHODS: Sixty patients presenting with acidotic (pH<7.35) acute, cardiogenic pulmonary oedema, were randomly assigned conventional oxygen therapy, CPAP (10 cm H(2)O), or bilevel ventilation (IPAP 15 cm H(2)O, EPAP 5 cm H(2)O) provided by a standard ventilator through a face mask. The main end points were treatment success at two hours and in-hospital mortality. Analyses were by intention to treat. RESULTS: Treatment success (defined as all of respiratory rate<23 bpm, oxygen saturation of>90%, and arterial blood pH>7.35 (that is, reversal of acidosis), at the end of the two hour study period) occurred in three (15%) patients in the control group, seven (35%) in the CPAP group, and nine (45%) in the bilevel group (p = 0.116). Fourteen (70%) of the control group patients survived to hospital discharge, compared with 20 (100%) in the CPAP group and 15 (75%) in the bilevel group (p = 0.029; Fisher's test). CONCLUSIONS: In this study, patients presenting with acute cardiogenic pulmonary oedema and acidosis, were more likely to survive to hospital discharge if treated with CPAP, rather than with bilevel ventilation or with conventional oxygen therapy. There was no relation between in hospital survival and early physiological changes. Survival rates were similar to other studies despite a low rate of endotracheal intubation.

Acidosis↗
PubMed2003

Defining "early dementia" and monitoring intervention: what measures are useful in family caregiving?

Measures of cognition are often used to define and measure the progress of dementia and outcomes of intervention. This paper examines whether measures of psychosocial disability used with those of cognition are more useful than measures of cognition alone, particularly in early dementia. A measure of cognition and two instruments of caregiver burden, used as routine clinical outcome measures of three types of Old Age Psychiatry dementia services, were examined. All cases with dementia in a memory clinic (MC; n = 149), a community mental health service for older people (CMHT; n = 120) and a specialist dementia day hospital (DH; n = 118), in one NHS district were followed up at 12 months. Measures of cognition (MMSE), behaviour, caregiver coping (Problem Checklist; PC) and caregiver mood (Hospital Anxiety and Depression Scale; HAD) were taken at baseline (MC, n = 48; CMHT, n = 113; DH, n = 55) and at follow-up (MC, n = 35; CMHT, n = 34; DH, n = 23). At baseline, all three groups had an average MMSE score of "mild impairment" but measures of behaviour and caregiver burden showed subtle between-group differences. At the 12-month follow-up, cognition remained stable in all groups, but the frequency of day-to-day problems increased and caregiver mood deteriorated in families receiving DH support. The use of psychosocial measures of disability in conjunction with those of cognition, are important in the definition and longitudinal measurement of intervention and support in early dementia.

Adaptation, Psychological↗
PubMed2003

Minimally invasive radioguided parathyroidectomy (MIRP).

The technique of parathyroidectomy has traditionally involved a bilateral exploration of the neck with the intent of visualizing 4 parathyroid glands and resecting pathologically enlarged glands. Parathyroid scanning using technetium-99m sestamibi has evolved and can now localize 80% to 90% of parathyroid adenomas. The technique of minimally invasive radioguided parathyroidectomy (MIRP) is a surgical option for most patients with primary hyperparathyroidism and a positive preoperative parathyroid scan. The technique makes use of a hand-held gamma probe that is used intraoperatively to guide the dissection in a highly directed manner with the procedure often performed under local anesthesia. The technique results in excellent cure rates while allowing most patients to leave the hospital within a few hours after the completion of the procedure. Current data also suggest the procedure can decrease hospital charges by approximately 50%. This technique may significantly change the management of primary hyperparathyroidism.

Equipment Design↗
PubMed2002

Acute normovolaemic haemodilution in colorectal surgery.

AIMS: Blood transfusions are often given to surgical patients. This study was designed to assess whether acute normovolaemic haemodilution (ANH) reduces exposure to allogeneic blood, affects clinical outcome and hospital stay, and is feasible in colorectal surgery. METHODS: All ASA 1 and 11 patients undergoing colectomies performed between 1997 and 1999 were identified retrospectively from our colorectal cancer database to ascertain our current peri and postoperative transfusion practice. Twenty-six selected patients subsequently underwent ANH during colectomy surgery. The number of patients and units transfused were identified. RESULTS: One hundred and twenty-three of 317 (39%) patients identified from our colorectal cancer database were transfused a total of 328 units (median 2, range 1-7). Of the 26 patients undergoing ANH, 4 (15%) were transfused a total of 13 units (median 3, range 2-5). The reduction in number of patients transfused was statistically significant (P=0.017). ANH increased anaesthetic time by a median of 19 min. There were no complications associated with ANH and the median hospital stay was 9 days (range 6-13). CONCLUSIONS: In this pilot study of selected patients, ANH is a feasible and effective method of reducing allogeneic blood exposure in major colorectal surgery. A prospective randomised controlled trial is now urgently required.

Adult↗
PubMed2001

Beet necrotic yellow vein virus particles localize to mitochondria during infection.

Fluorescent beet necrotic yellow vein virus (BNYVV) particles were produced by replacing part of the readthrough domain of the minor coat protein P75 with the green fluorescent protein (GFP). The recombinant virus was functional in plants and P75-GFP was incorporated at one end of the rod-shaped virions. Laser scanning confocal microscopy and transmission electron microscopy showed that virus-like particles, almost certainly authentic BNYVV virions, localized to the cytoplasmic surface of mitochondria at early times postinfection but relocated at later times to semiordered clusters in the cytoplasm. This is the first report of specific targeting of plant virus particles to the mitochondria in vivo.

Capsid↗
PubMed2001

Functional analysis of challenging behaviour in dementia: the role of superstition.

BACKGROUND: Intervention for challenging behaviour of residents living in care homes is a neglected area of research. Pharmacological methods of management are widespread, although support for their efficacy is, on the whole, poor. AIMS: There is little research on non-pharmacological methods of management and the present study aimed to add to the small literature in this area, by examining the meaning of behaviour for a given resident, within a functional analytic experimental framework. METHODS: The study involved a systematic manipulation of specific trigger situations to evaluate their influence on challenging behaviour, using a single case experimental design. RESULTS: Five residents with agitated and aggressive behaviour were successfully managed. The difficulties in engaging staff in the use of non-pharmacological, rather than pharmacological, methods and the scope for future randomised trials using psychological and environmental interventions to manage challenging behaviour, are discussed.

Aged↗
PubMed2001

Fungal infection of the diabetic foot: two distinct syndromes.

AIMS: Fungal infection of diabetic foot ulcers has not been described. We analysed the features of 17 patients with diabetic foot ulcers probably infected with fungi. METHODS: Seventeen patients were identified with clinically infected foot ulcers, (i) which had failed to heal despite prolonged antibiotic therapy and intensive podiatric care, (ii) from which Candida spp. was isolated or hyphae +/- yeasts were visualized in material from ulcers or surrounding skin. RESULTS: Multiple ulcers arising simultaneously were present in 10 patients (59%), preceded by blistering in seven cases. Single ulcers with markedly ulcerated margins were present in seven (41%) patients and were preceded by blisters in two. All 17 cases had neuropathy and 15 (88%) had severe peripheral vascular disease. All ulcers responded to antifungal therapy. CONCLUSIONS: Candida spp. is associated with two distinctive patterns of protracted ulceration in diabetic feet which improve following systemic antifungal therapy. Diabet. Med. 18, 567-572 (2001)

Adult↗
PubMed2000

P42 movement protein of Beet necrotic yellow vein virus is targeted by the movement proteins P13 and P15 to punctate bodies associated with plasmodesmata.

Cell-to-cell movement of Beet necrotic yellow vein virus (BNYVV) is driven by a set of three movement proteins--P42, P13, and P15--organized into a triple gene block (TGB) on viral RNA 2. The first TGB protein, P42, has been fused to the green fluorescent protein (GFP) and fusion proteins between P42 and GFP were expressed from a BNYVV RNA 3-based replicon during virus infection. GFP-P42, in which the GFP was fused to the P42 N terminus, could drive viral cell-to-cell movement when the copy of the P42 gene on RNA 2 was disabled but the C-terminal fusion P42-GFP could not. Confocal microscopy of epidermal cells of Chenopodium quinoa near the leading edge of the infection revealed that GFP-P42 localized to punctate bodies apposed to the cell wall whereas free GFP, expressed from the replicon, was distributed uniformly throughout the cytoplasm. The punctate bodies sometimes appeared to traverse the cell wall or to form pairs of disconnected bodies on each side. The punctate bodies co-localized with callose, indicating that they are associated with plasmodesmata-rich regions such as pit fields. Point mutations in P42 that inhibited its ability to drive cell-to-cell movement also inhibited GFP-P42 punctate body formation. GFP-P42 punctate body formation was dependent on expression of P13 and P15 during the infection, indicating that these proteins act together or sequentially to localize P42 to the plasmodesmata.

Amino Acid Sequence↗
PubMed2000

Effects of point mutations in the readthrough domain of the beet western yellows virus minor capsid protein on virus accumulation in planta and on transmission by aphids.

Point mutations were introduced into or near five conserved sequence motifs of the readthrough domain of the beet western yellows virus minor capsid protein P74. The mutant virus was tested for its ability to accumulate efficiently in agroinfected plants and to be transmitted by its aphid vector, Myzus persicae. The stability of the mutants in the agroinfected and aphid-infected plants was followed by sequence analysis of the progeny virus. Only the mutation Y201D was found to strongly inhibit virus accumulation in planta following agroinfection, but high accumulation levels were restored by reversion or pseudoreversion at this site. Four of the five mutants were poorly aphid transmissible, but in three cases successful transmission was restored by pseudoreversion or second-site mutations. The same second-site mutations in the nonconserved motif PVT(32-34) were shown to compensate for two distinct primary mutations (R24A and E59A/D60A), one on each side of the PVT sequence. In the latter case, a second-site mutation in the PVT motif restored the ability of the virus to move from the hemocoel through the accessory salivary gland following microinjection of mutant virus into the aphid hemocoel but did not permit virus movement across the epithelium separating the intestine from the hemocoel. Successful movement of the mutant virus across both barriers was accompanied by conversion of A59 to E or T, indicating that distinct features of the readthrough domain in this region operate at different stages of the transmission process.

Amino Acid Sequence↗
PubMed1999

Decreased memory performance in healthy humans induced by stress-level cortisol treatment.

BACKGROUND: Glucocorticoids (GCs) can regulate hippocampal metabolism, physiologic functions, and memory. Despite evidence of memory decreases during pharmacological GC treatment, and correlations between memory and cortisol levels in certain disease conditions, it remains unclear whether exposure to the endogenous GC cortisol at levels seen during physical and psychological stress in humans can inhibit memory performance in otherwise healthy individuals. METHODS: Randomized, double-blind, placebo-controlled comparison of 2 fixed oral doses of cortisol (40 mg/d and 160 mg/d using split doses to approximate circadian rhythm) given for 4 days to matched groups of healthy subjects (n = 51). Lower-dose treatment approximated cortisol exposure during mild stress, whereas the higher dose approximated cortisol exposure during major stress. Cognitive testing and plasma sampling were done at baseline, after 1 and 4 days of treatment, and after a 6-day washout period, hypothesizing dose-dependent decreases in verbal declarative memory. RESULTS: Cortisol treatment at the higher dose produced reversible decreases in verbal declarative memory without effects on nonverbal memory, sustained or selective attention, or executive function. A significant interaction between time and treatment condition for paragraph recall was explained by treatment-induced differences in performance after 4 treatment days, with lower immediate and delayed recall performance during higher-dose cortisol treatment compared with lower-dose treatment and placebo. CONCLUSIONS: Several days of exposure to cortisol at doses and plasma concentrations associated with physical and psychological stress in humans can-similar to pharmacological GC treatment-reversibly decrease specific elements of memory performance in otherwise healthy individuals.

Adult↗
PubMed1999

Association between - 308 tumour necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma.

BACKGROUND: Tumour necrosis factor (TNF) is a pivotal cytokine in the inflammation underlying asthma. The TNF gene is located in the polymorphic HLA class 3 region on chromosome 6p. Several polymorphisms in this region have been described and associated with alteration of TNF secretion in vitro. OBJECTIVE: In this study we tested the hypothesis that two such polymorphisms, lymphotoxin alpha NcoI B*1 and -308 TNF2 may be components of the genetic predisposition to asthma. METHODS: Five hundred and fifty-six random individuals were studied, comprising approximately equal numbers of asthmatic subjects, with or without atopy, and a nonatopic nonasthmatic control group. In addition, 355 subjects (172 asthmatics) from 60 multiplex families were typed at the LTalpha NcoI locus. RESULTS: There was an association between allele two of the -308 TNF polymorphism and bronchial hyperreactivity (OR 2.12, 95% CI 1.04-4.32, P = 0.036). However, there was no association with LTalpha NcoI alleles. To determine whether this was influenced by linkage disequilibrium within the MHC, 91 subjects with bronchial hyperreactivity and 85 control subjects were typed for class 2 and 3 alleles. Following identification of the extended TNF2 haplotype, we found no independent association of these alleles with BHR. CONCLUSIONS: We conclude that the -308 TNF2 promoter polymorphism may form a component of the genetic predisposition to BHR in asthma.

Adolescent↗
PubMed1998

Noninvasive pacing: what you should know.

Noninvasive pacing is a valuable therapy in emergency cardiac care. The more experience clinicians have with the noninvasive pacing procedure, the greater their confidence and the easier the job becomes. Effective troubleshooting during pacing becomes less problematic with increased experience with the therapy. Noninvasive pacing allows rapid initiation of emergency pacing and "buys time" to stabilize the patient and plan further care.

Arrhythmias, Cardiac↗
PubMed1998

A randomized trial of three iron dextran infusion methods for anemia in EPO-treated dialysis patients.

Forty-three hemodialysis patients receiving recombinant erythropoietin (rHuEPO, epoietin alpha) were randomized to receive intravenous iron dextran as a total-dose infusion, 500-mg infusion to total dose, or 100-mg bolus to total dose, in each case during the dialysis procedure. The dose of iron dextran was calculated from the patient's existing hemoglobin to achieve a desired hemoglobin. Patients were eligible to receive intravenous iron dextran if they had a serum ferritin of < or = 100 ng/mL or a serum ferritin of 100 to 200 ng/mL, along with a transferrin saturation of < or = 19%. Patients were excluded if they had prior therapy with iron dextran, aluminum intoxication, or transfusion during the study. The time to the maximum hemoglobin, acute adverse reactions, and delayed adverse reactions were analyzed statistically, and no differences were seen in any of the three groups. Total-dose intravenous iron dextran infusion is safe, convenient, less expensive, and as efficacious as divided-dose infusions.

Anemia↗