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Biomedical subjects

Peter D White

Publications and source records attributed to Peter D White.

At least 19 recordsLinked to original sources
PubMed2006

A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome.

BACKGROUND: Patients with chronic fatigue syndrome typically report high levels of physical activity before becoming ill. Few studies have examined premorbid and current activity levels in chronically fatigued patients. METHODS: In a case-control study, 33 patients with chronic, unexplained, disabling fatigue attending a university-based clinic specializing in fatigue were compared to 33 healthy, age- and sex-matched controls. Patients rated their activity levels before their illness and currently, using scales designed for this purpose. Controls reported their level of activity of 2 years previously and currently. Chi-square analyses, Student's t tests, and Wilcoxon signed rank tests were used in pair matched analyses. RESULTS: Compared to healthy controls, patients with chronic, unexplained fatigue rated themselves as more active before their illness (p < or = 0.001) and less active currently (p < or = 0.001). The patients also reported they currently stood or walked less than the controls (median [inter-quartile range] = 4 2345 versus 9 [7.5-12] hours, p < or = 0.001), and spent more time reclining (median [inter-quartile range] = 12 10111213141516 versus 8 [8-9.5] hours, p < or = 0.001). These differences remained significant for the subset of patients who met strict criteria for chronic fatigue syndrome or fibromyalgia. CONCLUSION: Patients with chronic, unexplained, disabling fatigue reported being more active before becoming ill than healthy controls. This finding could be explained by greater premorbid activity levels that could predispose to illness, or by an overestimation of previous activity. Either possibility could influence patients' perceptions of their current activity levels and their judgments of recovery. Perceived activity should be addressed as part of management of the illness.

Activities of Daily Living↗
PubMed2006

An empirical delineation of the heterogeneity of chronic unexplained fatigue in women.

OBJECTIVES: To test the hypothesis that medically unexplained chronic fatigue and chronic fatigue syndrome (CFS) are heterogeneous conditions, and to define the different conditions using both symptom and laboratory data. METHODS: We studied 159 women from KS, USA. A total of 51 of these suffered from fatigue consistent with established criteria for CFS, 55 had chronic fatigue of insufficient symptoms/severity for a CFS diagnosis and 53 were healthy controls matched by age and body mass index (BMI) against those with CFS. We used principal components analyses to define factors that best described the variable space and to reduce the number of variables. The 38 most explanatory variables were then used in latent class analyses to define discrete subject groups. RESULTS: Principal components analyses defined six discrete factors that explained 40% of the variance. Latent class analyses provided several interpretable solutions with four, five and six classes. The four-class solution was statistically most convincing, but the six-class solution was more interpretable. Class 1 defined 41 (26%) subjects with obesity and relative sleep hypnoea. Class 2 were 38 (24%) healthy subjects. Class 3 captured 24 (15%) obese relatively hypnoeic subjects, but with low heart rate variability and cortisol. Class 4 were 23 (14%) sleep-disturbed and myalgic subjects without obesity or significant depression. The two remaining classes with 22 (14%) and 11 (7%) subjects consisted of the most symptomatic and depressed, but without obesity or hypnoea. Class 5 had normal sleep indices. Class 6 was characterized by disturbed sleep, with low sleep heart rate variability, cortisol, and sex hormones. CONCLUSION: Chronic medically unexplained fatigue is heterogeneous. The putative syndromes were differentiated by obesity, sleep hypnoea, depression, physiological stress response, sleep disturbance, interoception and menopausal status. If these syndromes are externally validated and replicated, they may prove useful in determining the causes, pathophysiology and treatments of CFS.

Adult↗
PubMed2006

The validity of an empirical delineation of heterogeneity in chronic unexplained fatigue.

OBJECTIVES: To validate a latent class structure derived empirically from a clinical data set obtained from persons with chronic medically unexplained fatigue. METHODS: The strategies utilized in this validation study included: recalculating latent class analysis (LCA) results varying random seeds and the number of initial random starting sets; recalculating LCA results by substituting alternate variables to demonstrate a robust solution; determining the statistical significance of between-class differences on disability, fatigue and demographic measures omitted from the data set used for LCA; cross-classifying class membership using established Centers for Disease Control and Prevention (CDC) research criteria for chronic fatigue syndrome (CFS) to compare the relative proportions of subjects designated CFS, chronic fatigue (not CFS) or healthy controls captured by the latent classes. RESULTS: Recalculation of results and substitution of variables for low-loading variables demonstrated a robust LCA result. Highly significant between-class differences were confirmed between Class 2 (well) and those interpreted as ill/fatigued. Analysis of between-class differences for the fatigue groups revealed significant differences for all disability and fatigue variables, but with equivalent levels of reported activity and reduction in motivation. Cross-classification against established CDC criteria demonstrated that 89% of subjects constituting Class 2 (well) were indeed nonfatigued controls. A general tendency for grouping CFS cases in the multiple symptomatic classes was noted. CONCLUSION: This study established reasonably good validity for an empirically-derived latent class solution reflecting considerable heterogeneity among subjects with medically unexplained chronic fatigue. This work strengthens the growing understanding of CFS as a heterogeneous entity comprised of several conditions with different underlying pathophysiological mechanisms.

Adult↗
PubMed2006

Gene expression profile of empirically delineated classes of unexplained chronic fatigue.

OBJECTIVES: To identify the underlying gene expression profiles of unexplained chronic fatigue subjects classified into five or six class solutions by principal component (PCA) and latent class analyses (LCA). METHODS: Microarray expression data were available for 15,315 genes and 111 female subjects enrolled from a population-based study on chronic fatigue syndrome. Algorithms were developed to assign gene scores and threshold values that signified the contribution of each gene to discriminate the multiclasses in each LCA solution. Unsupervised dimensionality reduction was first used to remove noise or otherwise uninformative gene combinations, followed by supervised dimensionality reduction to isolate gene combinations that best separate the classes. RESULTS: The authors' gene score and threshold algorithms identified 32 and 26 genes capable of discriminating the five and six multiclass solutions, respectively. Pair-wise comparisons suggested that some genes (zinc finger protein 350 [ZNF350], solute carrier family 1, member 6 [SLC1A6], F-box protein 7 [FBX07] and vacuole 14 protein homolog [VAC14]) distinguished most classes of fatigued subjects from healthy subjects, whereas others (patched homolog 2 [PTCH2] and T-cell leukemia/lymphoma [TCL1A]) differentiated specific fatigue classes. CONCLUSION: A computational approach was developed for general use to identify discriminatory genes in any multiclass problem. Using this approach, differences in gene expression were found to discriminate some classes of unexplained chronic fatigue, particularly one termed interoception.

Algorithms↗
PubMed2006

Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue.

Chronic fatigue syndrome (CFS) is characterized by persistent or relapsing fatigue that is not alleviated by rest, causes substantial reduction in activities and is accompanied by a variety of symptoms. Its unknown etiology may reflect that CFS is heterogeneous. Latent class analyses of symptoms and physiological systems were used to delineate subgroups within a population-based sample of fatigued and nonfatigued subjects [1] . This study examined whether genetic differences underlie the individual subgroups of the latent class solution. Polymorphisms in 11 candidate genes related to both hypothalamic-pituitary-adrenal (HPA) axis function and mood-related neurotransmitter systems were evaluated by comparing each of the five ill classes (Class 1, n = 33; Class 3, n = 22; Class 4, n = 22; Class 5, n = 17; Class 6, n = 11) of fatigued subjects with subjects defined as well (Class 2, n = 35). Of the five classes of subjects with unexplained fatigue, three classes were distinguished by gene polymorphsims involved in either HPA axis function or neurotransmitter systems, including proopiomelanocortin (POMC), nuclear receptor subfamily 3, group C, member 1 (NR3C1), monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), and tryptophan hydroxylase 2 (TPH2). These data support the hypothesis that medically unexplained chronic fatigue is heterogeneous and presents preliminary evidence of the genetic mechanisms underlying some of the putative conditions.

Affect↗
PubMed2005

The prognosis of different fatigue diagnostic labels: a longitudinal survey.

BACKGROUND: Several different diagnostic labels exist for the fatigue syndromes, including chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME) and postviral fatigue syndrome (PVFS). An allied condition is fibromyalgia. No study has examined prognostic differences across these different labels. OBJECTIVE: To compare the prognoses of patients labelled with different fatigue syndromes in primary care. METHODS: We performed a longitudinal survey, using electronic records from the General Practice Research Database. All 18,122 patients diagnosed by their GP with a fatigue syndrome from 1988-2001 with a minimum of one year of records after diagnosis were collated into four groups: CFS, ME, PVFS and fibromyalgia. CFS and ME were combined for the main analysis as no code for CFS was available until 1995. The length of illness was calculated as the interval between the diagnosis and the last recorded fatigue symptom, expressed as days per year, to account for differing lengths of record after diagnosis. RESULTS: Patients with CFS/ME combined had a worse prognosis (median length of illness 80 days per year; interquartile range 0-242) than fibromyalgia (51; 0-244) or PVFS 0 (0-108), a significant difference, P < 0.001. In a subgroup analysis, ME had a worse prognosis (median length of illness in days per year 106; interquartile range 0-259) than CFS (33; 0-170), P < 0.001, in spite of a better course before diagnosis. Secondary outcome measures were consistent with these results. CONCLUSION: There were important differences in outcome between the various fatigue labels, with ME having the worst prognosis and PVFS the best. This could be an adverse effect of the label ME itself. Alternatively, patients who are destined to have a worse prognosis may preferentially attract the ME label. Our data support the first interpretation.

Adult↗
PubMed2005

PS-COD and PS-9-BBN: polymer-supported reagents for solution-phase parallel synthesis.

1,5-Cyclooctadiene was deprotonated under LICKOR conditions and reacted with Merrifield resin to afford an immobilized cyclooctadiene in high yield. This polymer is effective as a halogen scavenger, while hydroboration leads to a supported 9-BBN analogue. The latter exhibits similar regioselectivity to 9-BBN in olefin hydroboration. [reaction: see text]

Alkenes↗
PubMed2005

Chronic upper limb pain: an exploration of the biopsychosocial model.

OBJECTIVE: To model pain intensity and consequent disability by independent physical, psychological, and social variables in a group of patients with chronic upper limb pain. METHODS: We studied a group of 73 hospital outpatients with either chronic work related diffuse upper limb pain or carpal tunnel syndrome. We assessed pain intensity, disability, and personality by self-rated questionnaires; and psychiatric morbidity by a standardized interview. We measured illness behavior by assessing coping strategies, illness beliefs, financial benefits, and movements of the most affected limb. RESULTS: In both pain conditions, disability was positively correlated with present pain intensity, depression, helpless coping style, and receipt of state financial benefits; and was negatively correlated with age. This explained 43% of the variance and correctly classified 85% of all patients. Present pain intensity was positively correlated with both depression and the number of arm movements at night. This model explained 15% of the variance and correctly classified 75% of all patients. Inclusion of diagnostic group has no effect on these models. CONCLUSION: The correlations between disability and pain intensity with both psychosocial and physical factors support the biopsychosocial model of disability in particular, and pain to a lesser extent, irrespective of the diagnosis.

Adolescent↗
PubMed2004

Polymer-supported O-alkylisoureas: useful reagents for the O-alkylation of carboxylic acids.

Polymer-supported O-alkylisoureas were prepared by reaction of an alcohol with a polymer-supported carbodiimide under copper(II) catalysis. These reagents were used to transform carboxylic acids into the corresponding methyl, benzyl, allyl, and p-nitrobenzyl esters in a highly chemoselective manner in high yields and in very high purity after simple resin filtration and solvent evaporation. The reactions could be carried out using both conventional or microwave heating, with reaction times as short as 3-5 min in the latter case, without compromising yield, purity, or chemoselectivity. Unfortunately, the corresponding solid-supported tert-butyl isoureas could not be prepared.

Journal Article↗
PubMed2004

Self-indicating amine scavenger resins.

Self-indicating methylisocyanate resin, which functions as both a scavenger and an indicator for amines, was used for in-situ reaction monitoring and purification of a urea based library.

Journal Article↗
PubMed2004

Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001.

Little is known about whether the incidence of symptoms of fatigue presented in primary care, and the consequent diagnoses made, change over time. The UK General Practice Research Database was used to investigate the annual incidence of both fatigue symptoms and diagnoses recorded in UK primary care from 1990 to 2001. The overall incidence of all fatigue diagnoses decreased from 87 per 100 000 patients in 1990 to 49 in 2001, a reduction of 44%, while postviral fatigue syndromes decreased from 81% of all fatigue diagnoses in 1990 to 60% in 2001. Chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) together increased from 9% to 26% of all fatigue diagnoses. The incidence of fibromyalgia increased from less than 1 per 100 000 to 35 per 100 000. In contrast, there was no consistent change in the incidence of all recorded symptoms of fatigue, with an average of 1503 per 100 000, equivalent to 1.5% per year. CFS/ME and fibromyalgia were rarely diagnosed in children and were uncommon in the elderly. All symptoms and diagnoses were more common in females than in males. The overall incidence of fatigue diagnoses in general has fallen, but the incidence rates of the specific diagnoses of CFS/ME and fibromyalgia have risen, against a background of little change in symptom reporting. This is likely to reflect fashions in diagnostic labelling rather than true changes in incidence.

Adult↗
PubMed2003

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.

BACKGROUND: Chronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance. METHODS: Experienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here. RESULTS: Ambiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability. CONCLUSION: This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

Cognition↗
PubMed2003

Polymer-supported o-benzyl and o-allylisoureas: convenient preparation and use in ester synthesis from carboxylic acids.

[reaction: see text] Polymer-supported O-methyl, O-benzyl, and O-allyl-isoureas were prepared by copper(II)-catalyzed reaction of polymer-supported carbodiimide with the corresponding alcohols. These polymer-supported reagents were successfully employed to convert a series of carboxylic acids to methyl, benzyl, or allyl esters, in good yields. The products were obtained with high purity (>95% by NMR) after a simple resin filtration-solvent evaporation sequence.

Journal Article↗
PubMed2003

Illness behavior and psychosocial factors in diffuse upper limb pain disorder: a case-control study.

OBJECTIVE: To compare behavioral and other psychosocial factors in patients with diffuse upper limb pain disorder (ULPD) and patients with carpal tunnel syndrome (CTS). METHODS: We compared 37 hospital outpatients with diffuse ULPD with 36 hospital outpatients with CTS, matched by sex, pain intensity, and duration of illness. We assessed psychiatric morbidity by a standardized interview, and both symptoms and personality by self-rated questionnaires. We measured illness behavior by assessing financial benefits and compensation, coping strategies, illness beliefs, treatments received, and 24 hours of monitoring movements of the most affected arm and the body as a whole. RESULTS: There were no significant differences in the prevalence of either current or premorbid psychiatric disorders, personality scores, symptom amplification, disability, or treatments received. Subjects with ULPD had significantly lower self-rated scores for depression, somatic distress, sleep disturbance, and physical fatigue than subjects with CTS, although there were more than normal levels of anxiety, fatigue, and sleep disturbance in both groups. There were no significant differences in the numbers of arm or body movements by day and night. Significantly more ULPD subjects had been involved in litigation, but litigating patients were a minority. CONCLUSION: The primary etiology of endemic diffuse ULPD, presenting in secondary care, is no more psychiatric, psychological, behavioral, or related to personality than is the case with a similarly chronic and painful condition of known pathology. We cannot exclude either a specific role for psychosocial factors at work, or a more general role for psychosocial factors in maintaining disability in patients with chronic pain.

Adaptation, Psychological↗
PubMed2002

Microwave-accelerated O-alkylation of carboxylic acids with O-alkylisoureas.

[reaction: see text] Microwave-assisted O-alkylations of several carboxylic acids have been performed with three different O-alkylisoureas. All reactions are significantly faster compared to conventionally heated reactions, while retaining high chemoselectivity. The combination of microwave technology with the use of the solid-supported isourea 3 enables the synthetic chemist to obtain the pure methyl esters starting from the corresponding acids in less than an hour.

Journal Article↗