Wilms' tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML.
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Acute Disease↗
Biomedical subjects
J Stevens
Publications and source records attributed to J Stevens.
Auditory temporal processing deficits in patients with insular stroke.
OBJECTIVE: To assess central auditory function in a series of patients with stroke of the insula and adjacent areas. METHODS: The authors recruited eight patients with stroke affecting the insula and adjacent areas and eight neurologically normal controls (matched to the patients for age, sex, handedness, and hearing thresholds). The lesion spared the adjacent auditory areas in three patients and included other auditory structures in five cases. The authors conducted pure-tone audiometry and tympanometry and a central auditory test battery, which included the dichotic digits, and three temporal tests, the duration pattern, frequency pattern, and gaps in noise tests. They collected information from the hospital notes on symptoms at presentation and neuropsychological assessment data during the acute phase. RESULTS: The central auditory tests gave normal results in all controls. The temporal tests gave abnormal results in all three cases in which other auditory areas were spared, as well as in the other five cases. Results of the gaps in noise test were abnormal contralaterally to the lesion in three and bilaterally in five cases. The central auditory deficits did not cosegregate with the presence of cognitive impairment during the acute stage. CONCLUSION: Insular lesions may affect central auditory function and, in particular, temporal resolution and sequencing, consistent with neuroimaging studies.
Adult↗
Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
OBJECTIVE: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? METHODS: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. RESULTS, CONCLUSIONS, AND RECOMMENDATIONS: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).
Dyskinesias↗
Expression of the calcium receptor in human breast cancer--a potential new marker predicting the risk of bone metastases.
AIMS: This study investigates whether the calcium-sensing receptor (CaR) is commonly expressed in primary breast cancers. The CaR controls secretion of PTHrP in several breast cancer cell lines and PTHrP is known to stimulate osteolysis during metastatic bone resorption. Whether this could explain the propensity of breast cancers to develop bone metastases has not been explored. METHODS: With Ethical Committee approval, immunohistochemistry was performed using a commercially available antiCaR antibody (AffinityBioReagents, Cambridge, UK) on archived histological sections of primary tumours from patients who died with advanced breast cancer. Intensity of CaR expression was assessed by two independent observers on a 6-point scale. RESULTS: One hundred and eight patients with breast cancer were found to have positive bone scans, 42 patients had died. Of the patients with negative bone scans, 23 had liver or lung metastases. Most patients with strongly expressed CaR (score 4-5 on immunohistochemistry) had bone metastases (13/15 patients) compared with 2/23 patients with normal bone scans (p < 0.001, chi(2) test). Other clinical/pathological markers (ER, PR, c-erb B-2, LN status) were not significantly different between patients with CaR-positive or CaR-negative tumours. CONCLUSIONS: CaR expression is common in a selected group of patients with advanced primary breast cancers. A prospective study should investigate if patients with CaR-positive tumours are more likely to develop bone metastases.
Adult↗
Changes in risk factors for cardiovascular disease by baseline weight status in young adults who maintain or gain weight over 15 years: the CARDIA study.
OBJECTIVES: To examine whether changes in cardiovascular disease (CVD) risk factors differ by baseline weight status among young adults who maintained or gained weight. DESIGN: Longitudinal cohort study. SUBJECTS: White and African Americans who either maintained (+/-5 pounds; n=488) or gained (>5 pounds; n=2788) weight over 15 years. MEASUREMENTS: Anthropometrics and CVD risk factors were measured at baseline (1985-1986) and follow-up. Participants were classified as normal weight (body mass index (BMI) 18.5-24.9 kg/m2) or overweight (BMI >or=25 kg/m2) at baseline. Multivariable models were stratified by ethnicity and weight change category. RESULTS: Normal weight maintainers tended to have more favorable risk factors at baseline and follow-up than overweight maintainers. Size and direction of 15-year changes in risk factors were similar by weight status, except that in white normal weight maintainers changes in high-density lipoprotein (HDL)-cholesterol (3.3 mg/dl (95% confidence interval (CI): 0.4, 6.3)) and triglycerides (-14.7 mg/dl (-25.8, -3.7)) were more favorable. Weight gain was associated with unfavorable changes in risk factors. Weight gainers normal weight at baseline had less adverse changes in glucose, blood pressure, HDL-cholesterol (whites only) and triglycerides (African Americans only) than overweight gainers. However, normal weight African-American weight gainers had more adverse changes in total (3.1 mg/dl (0.2, 6.1)) and low-density lipoprotein-cholesterol (3.4 mg/dl (0.6, 6.3)). CONCLUSIONS: Baseline weight status does not appear to influence the size or direction of risk factor changes among adults who maintained their weight over 15 years. In contrast, weight gain was associated with changes in some risk factors differentially by baseline weight status.
Adolescent↗
The definition of weight maintenance.
There is currently no consensus on the definition of weight maintenance in adults. Issues to consider in setting a standard definition include expert opinion, precedents set in previous studies, public health and clinical applications, comparability across body sizes, measurement error, normal weight fluctuations and biologic relevance. To be useful, this definition should indicate an amount of change less than is clinically relevant, but more than expected from measurement error or fluctuations in fluid balance under normal conditions. It is an advantage for the definition to be graded by body size and to be easily understood by the public as well as scientists. Taking all these factors into consideration, the authors recommend that long-term weight maintenance in adults be defined as a weight change of <3% of body weight.
Body Mass Index↗
Increased sensitivity to pathological brain changes using co-registration of magnetic resonance imaging scans.
PURPOSE: To compare automatic software-based co-registration of serial magnetic resonance imaging (MRI) scans with conventional visual comparison, by expert neuroradiologists. MATERIAL AND METHODS: Sixty-four patients who were referred to our epilepsy MRI unit for cerebral imaging were identified as having potentially, non-, or slow-growing lesions or cerebral atrophy and followed with sequential scans over a period of up to 8 years, resulting in a total of 92 pairs of scans. Scans were categorized as showing either lesions or atrophy. Each pair of scans was reviewed twice for the presence of change, with and without co-registration, performed using automated software. RESULTS: Co-registration and visual reporting without co-registration were discordant in the lesions group in nine out of 69 datasets (13%), and in 16 out of 23 pairs of scans in the atrophy group (69%). The most common cause of discordance was visual reporting not detecting changes apparent by co-registration. In three cases, changes detected visually were not detected following co-registration. CONCLUSION: In the group of patients studied, co-registration was more sensitive for detecting changes than visual comparison, particularly with respect to atrophic changes of the brain. With the increasing availability of sophisticated independent consoles attached to MRI scanners that may be used for image co-registration, we propose that serial T1-weighted volumetric MRI brain co-registration should be considered for integration into routine clinical practice to assess patients with suspected progressive disease.
Atrophy↗
Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel's opinion and review of the literature.
BACKGROUND: The use of dampened bandages to reduce inflamed eczema (synonyme dermatitis) is an old remedy. In order to evaluate the current indications for so-called wet-wrap treatment (WWT) for atopic dermatitis (AD), and to compare the different currently recognized methods, a group of experts critically reviewed their own expertise on WWT in respect to the existing literature on the subject. RESULTS: WWT is well tolerated in eczema due to the cooling effect on the skin and the rapid improvement in skin inflammation. It has been shown to be an extremely effective treatment for acute erythrodermic dermatitis, therapy-resistant AD and intolerable pruritus. Advantages of WWT include rapid response to therapy, reduction in itch and sleep disturbance, and potential for reduction in usage of topical corticosteroids (TCS). However, disadvantages include high cost, the necessity for special training in usage, potential for increased TCS absorption, increased cutaneous infections and folliculitis, and poor tolerability. Precautions to reduce the risks of long-term treatment should include education, monitoring of weight and height and, if necessary, serum cortisol levels. In adolescents the risk of striae from TCS absorption around puberty is high, and WWT with TCS in this age group should be used as a short-term therapy only and with extreme caution. To reduce risks, dilutions of steroids may be used ranging from 5 to 10%. In the maintenance phase this treatment can be rotated with the use of emollients only. Low potency TCS should be used on the face (with a mask). CONCLUSION: WWT using diluted steroids is a relatively safe addition to the therapeutic treatment options for children and adults with severe and/or refractory AD. Explanation and education is extremely important in the treatment of AD and WWT should only be employed by practitioners trained in its use. Specialized nursing care is essential, especially when using WWT for prolonged periods.
Bandages↗
The isoflavone genistein inhibits LPS-stimulated TNFalpha, but not IL-6 expression in monocytes from hemodialysis patients and healthy subjects.
BACKGROUND: Whole blood and peripheral blood mononuclear cells from hemodialysis (HD) patients show increased production and secretion of inflammatory cytokines. We determined the contribution of blood monocytes to the production of inflammatory cytokines in whole blood from HD patients. METHODS: Whole blood and isolated mononuclear cells from HD patients and healthy control subjects were preincubated with the isoflavone genistein and stimulated with LPS. TNFalpha, IL-6 and IL-10 formation in the whole blood was measured with ELISA and intracellular cytokine formation in CD 14-positive monocytes was determined by flow cytometry. RESULTS: Unstimulated blood levels of TNFalpha, IL-6 and IL-10 were significantly elevated in HD patients compared to controls, but intracellular monocyte content of these cytokines was identical between groups. LPS induced a robust TNFalpha response in both whole blood and monocytes, and TNFalpha formation was 2.3-fold higher in blood from HD patients compared to controls. A similar trend was observed in monocytes. Conversely, LPS stimulation increased IL-6 levels >1000-fold in whole blood, albeit without a noticeable difference between groups. Only minor increases in monocyte IL-6 content were observed. The isoflavone genistein did not inhibit IL-6 formation and did not alter basal TNFalpha levels, but genistein selectively blocked LPS-induced TNFalpha formation in whole blood and monocytes from both groups. CONCLUSION: Intracellular levels of TNFalpha, IL-6 and IL-10 in monocytes are indistinguishable between HD patients and healthy controls. However, monocytes from HD patients are selectively primed for enhanced TNFalpha secretion in response to LPS. The selective inhibition of monocyte TNFalpha production by genistein may explain the anti-inflammatory action of this phytochemical observed in vivo.
Adult↗
Abdominal fat distribution and functional limitations and disability in a biracial cohort: the Atherosclerosis Risk in Communities Study.
OBJECTIVE: To examine the associations of abdominal fat and obesity with functional limitations and disability in late adulthood. DESIGN: Longitudinal, cohort study. PARTICIPANTS: African American and white men and women aged 45-64 y at baseline with measured waist circumference, waist-to-hip ratio (WHR), and body mass index (BMI) who participated in the Atherosclerosis Risk in Communities (ARIC) Study (n = 9416). OUTCOME MEASURES: Self-reported functional limitations, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) at ages 52-75 y. RESULTS: Waist circumference, WHR, and BMI were positively associated with functional limitations and ADL and IADL impairment approximately 9 y later among African American and white men and women. For example, in African American women the odds ratios (95% CI) associated with a one standard deviation (s.d.) increment in waist circumference (13.3 cm) for severe functional limitations and ADL and IADL impairment were 2.36 (2.00-2.79), 1.41 (1.25-1.58), and 1.49 (1.34-1.66), respectively. In white women, the odds ratios (95% CI) were 2.66 (2.39-2.96), 1.60 (1.47-1.74), and 1.42 (1.31-1.53), respectively. Similar associations were found in men. A 1 s.d. increment in WHR (0.08 U) and BMI (5.06 kg/m2) produced similar results. The associations of waist circumference and WHR with functional limitations and ADL and IADL impairment were attenuated but, in general, remained statistically significant when BMI was added to the models. CONCLUSIONS: Maintaining a healthy body weight and avoiding increases in abdominal fat should be investigated for their potential to reduce the risk of functional limitations and disability in an aging population.
Abdominal Fat↗
Knowing your nose better than your thumb: measures of over-grasp reveal that face-parts are special for grasping.
Typically, when a grasping response is made, the hand opens wider than the target object. We show that this "over-grasp" response is reduced when we reach to parts of our own face, relative to when we reach to other body parts or to neutral objects. This is not due to reaching to different parts of body space, as over-grasp responses are indifferent to whether or not other body parts or neutral objects are placed close to the face. It is also not due to differences in perceptual knowledge of the size of the target object. We conclude instead that the familiarity of face parts influences the grasping response directly. Subsequent experiments demonstrate that the movement representation determining any effect is not based on a torso-centred frame, and not abstracted from the specific hand used for grasping. We discuss the implications of the results for understanding and measuring motor representations for familiar actions.
Adolescent↗
Associations of fitness and fatness with mortality in Russian and American men in the lipids research clinics study.
OBJECTIVE: To examine the relative size of the effects of fitness and fatness on mortality in Russian men, and to make comparison to US men. DESIGN: Prospective closed cohort. SUBJECTS: 1359 Russian men and 1716 US men aged 40-59 y at baseline (1972-1977) who were enrolled in the Lipids Research Clinics Study. MEASUREMENTS: Fitness was assessed using a treadmill test and fatness was assessed as body mass index (BMI) calculated from measured height and weight. Hazard ratios were calculated using proportional hazard models that included covariates for age, education, smoking, alcohol intake and dietary keys score. All-cause and cardiovascular disease (CVD) mortality were assessed through 1995. RESULTS: In Russian men, fitness was associated with all-cause and CVD mortality, but fatness was not. For mortality from all causes, compared to the fit-not fat, the adjusted hazard ratios were 0.87 (95% CI: 0.55, 1.37) among the fit-fat, 1.86 (95% CI: 1.31, 2.62) among the unfit-not fat and 1.68 (95% CI: 1.06, 2.68) among the unfit-fat. Among US men, the same hazard ratios were 1.40 (95% CI: 1.07, 1.83), 1.41 (95% CI: 1.12, 1.77) and 1.54 (95% CI: 1.24, 2.06), respectively. There were no statistically significant interactions between fitness and fatness in either group of men for all-cause or CVD mortality. CONCLUSION: The effects of fitness on mortality may be more robust across populations than are the effects of fatness.
Adult↗
Long-term follow up of sequential mobilisation and autologous transplantation with CD34-selected cells in multiple myeloma: a multimodality approach.
BACKGROUND: Even after high dose chemotherapy (HDT) and autologous haemopoietic stem cell transplantation, the majority of patients with multiple myeloma eventually relapse. AIM: The aim of the present study was to study the -feasibility and outcome of delivering a regimen including in vivo and in vitro purging and double HDT in patients with multiple myeloma. METHODS: Thirty-four patients with advanced multiple myeloma were enrolled in a program of vincristine, doxorubicin and dexamethasone chemotherapy, high dose cyclophosphamide/granulocyte macrophage colony stimulating factor (GM-CSF) stem cell mobilisation, CD34 selection of harvested stem cells (in vitro purging), double HDT (cyclophosphamide/epirubicin in the first, busulphan/melphalan in the second) rescued by CD34(+)-selected cells, the second rescue using cells harvested following the first HDT (in vivo purging) and interferon maintenance. RESULTS: Forty-four per cent of patients completed the program. Fifty-three per cent of withdrawals were as a result of insufficient stem cells. This correlated to previous chemotherapy. Therapy-related mortality was 6%. CD34(+) selection achieved more than a 2-log reduction of CD38(++) cells; in vivo purging achieved 80%. Although similar numbers of CD34(+) cells were reinfused at both HDT, platelet recovery was slower after the second HDT. Additional complete remissions were achieved after each phase of therapy, 3% at the end of vincristine, doxorubicin and dexamethasone and 33% after completing planned HDT. Factors associated with longer overall survival included age less than 60 years (P = 0.044), serum beta-2-microglobulin below 3 micro gamma/L at entry (P = 0.042) and less than 2 months between the two HDT (P = 0.024). The only factor associated with a longer event-free survival was less than 2 months between HDT on study (P = 0.038). CONCLUSIONS: (i) dose intensification with two HDT delivered within 2 months might be associated with a better patient outcome, (ii) early mobilisation should be incorporated in multiple myeloma HDT programs and (iii) higher CD34(+) doses may be required for tandem transplants.
Adult↗
Diagnosis, assessment and management of mixed aetiology ulcers using reduced compression.
Accurate diagnosis of mixed aetiology leg ulcers depends on detailed assessment by a trained practitioner. This paper, the fourth in a six-part series on leg ulcers, describes how reduced compression bandaging can achieve successful outcomes.
Bandages↗
The magic measurement.
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Alzheimer Disease↗
Quantitative MRI detects abnormalities in relatives of patients with epilepsy and malformations of cortical development.
Malformations of cortical development (MCD) are a common etiology for epilepsy. Laminar heterotopia, bilateral subependymal heterotopia, and lissencephaly have a genetic basis. No gene mutations have yet been identified in patients with focal cortical dysplasias. The aim of this study was to use quantitative morphometric tools to determine if there were gray matter abnormalities in relatives of patients with MCD. We studied 19 relatives of 13 probands with MCD and 58 healthy controls with high-resolution MRI. The relatives and controls had no neocortical abnormalities on visual inspection. MRI data were analyzed with voxel-based morphometry and autoblock analysis. Voxel-based morphometry showed significant increases of gray matter in 9 of 10 probands, 5 of 19 relatives, and 5 of 58 controls. The autoblock analysis showed significant abnormalities in 7 of 8 probands, 8 of 19 relatives, and 2 of 57 controls. This finding suggests structural abnormality in the brains of a greater number of relatives of MCD patients than would be expected, and in the context, a reasonable inference is that this reflects subtle genetically determined cerebral abnormalities, although acquired pathologies are possible and are not excluded.
Adolescent↗
Ethnic-specific cutpoints for obesity vs country-specific guidelines for action.
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Body Mass Index↗
Ethnic-specific revisions of body mass index cutoffs to define overweight and obesity in Asians are not warranted.
Studies showing that Asians with a body mass index (BMI) at the high end of the 'normal' range are at increased risk of disease do not justify a different definition of obesity for that ethnic group without comparable data from Caucasians showing no similar increase in risk. The current BMI cutpoints for obesity are somewhat arbitrary, but there is value in a simple, uniform definition across populations. It seems prudent to separate the scientific construct of obesity from the politically linked, nationally specific BMI cutpoint used to trigger public health or clinical action.
Asian People↗