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Biomedical subjects

D Buchwald

Publications and source records attributed to D Buchwald.

At least 19 recordsLinked to original sources

The nosology of sub-acute and chronic fatigue syndromes that follow infectious mononucleosis.

BACKGROUND: A previous principal components analysis of symptoms occurring after infectious mononucleosis suggested that a discrete fatigue syndrome occurs, which is independent of psychiatric disorder. This work has not been replicated and no latent class analysis of subjects has been published. METHOD: We prospectively examined a cohort of 150 American primary care patients 2 and 6 months after the onset of corroborated infectious mononucleosis. A subset of 50 subjects was studied 4 years after onset. We performed principal components analyses of both psychological and somatic symptoms and latent class analyses of subjects. RESULTS: Principal components analyses consistently delineated two fatigue factors at 2 and 6 months and one fatigue factor at 4 years. These factors were separate from a mixed anxiety and depressive factor. A four-class solution for the latent class analyses consisted of most subjects with few symptoms, a few with many symptoms, a group with predominantly mood symptoms and some subjects with fatigue symptoms. CONCLUSIONS: The symptoms of the principal factors with fatigue were similar to those previously described. Both the factors and classes were independent of an equally delineated mood factor and class. These results support the existence of two discrete chronic fatigue syndromes after infectious mononucleosis, one of which is still demonstrable 4 years after onset.

Acute Disease↗

Post-traumatic stress disorder among patients with chronic pain and chronic fatigue.

BACKGROUND: Fibromyalgia (FM), a chronic pain condition of unknown aetiology often develops following a traumatic event. FM has been associated with post-traumatic stress disorder (PTSD) and major depression disorder (MDD). METHOD: Patients seen in a referral clinic (N=571) were evaluated for FM and chronic fatigue syndrome (CFS) criteria. Patients completed questionnaires, and underwent a physical examination and a structured psychiatric evaluation. Critical components of the diagnostic criteria of FM (tender points and diffuse pain) and CFS (persistent debilitating fatigue and four of eight associated symptoms) were examined for their relationship with PTSD. RESULTS: The prevalence of lifetime PTSD was 20% and lifetime MDD was 42%. Patients who had both tender points and diffuse pain had a higher prevalence of PTSD (OR=3.4, 95% CI 2.0-5.8) compared with those who had neither of these FM criteria. Stratification by MDD and adjustment for sociodemographic factors and chronic fatigue revealed that the association of PTSD with FM criteria was confined to those with MDD. Patients with MDD who met both components of the FM criteria had a three-fold increase in the prevalence of PTSD (95% CI 1.5-7.1); conversely, FM patients without MDD showed no increase in PTSD (OR=1.3, 95% CI 0.5-3.2). The components of the CFS criteria were not significantly associated with PTSD. CONCLUSION: Optimal clinical care for patients with FM should include an assessment of trauma in general, and PTSD in particular. This study highlights the importance of considering co-morbid MDD as an effect modifier in analyses that explore PTSD in patients with FM.

Adolescent↗

Latent class analysis of symptoms associated with chronic fatigue syndrome and fibromyalgia.

BACKGROUND: Chronic fatigue syndrome and fibromyalgia continue to be perplexing conditions of unknown validity. Aetiological and symptomatic heterogeneity is likely and the distinctiveness of these disorders remains unclear. Our aims were to investigate empirically symptomatic heterogeneity in chronic fatigue syndrome and fibromyalgia. METHODS: Latent class analysis was applied to data from 646 patients who met accepted criteria for chronic fatigue syndrome and/or fibromyalgia who were systematically evaluated at a specialist fatigue clinic. Thirty-two symptoms commonly found in chronic fatigue syndrome and fibromyalgia were entered into the latent class analysis. RESULTS: We chose to interpret a four class solution. The classes appeared to differ in a graded fashion (rather than qualitatively) for symptom endorsements, pre-morbid characteristics, and co-morbidity with panic disorder and major depression. CONCLUSIONS: These results were unexpected given the usual assumption of the distinctiveness of chronic fatigue syndrome and fibromyalgia. These results support a conceptualization of chronic fatigue syndrome and fibromyalgia as being characterized by greater similarities than differences.

Adult↗

Brain SPECT: a controlled, blinded assessment of intra-reader and inter-reader agreement.

A detailed assessment of intra- and inter-reader variation in the interpretation of brain SPECT scans has been performed. A random sample was selected from scans performed at a community/teaching hospital in Seattle. Scans were interpreted independently by three experienced readers who were blinded to all patient information. Forty-eight scans were interpreted twice by each reader, for a total of 288 readings. Readers recorded detailed assessments of individual lesions and overall impressions using a standardized reporting form. Intra-observer agreement as reflected in per cent agreement for severity scores ranged from 65% to 100%. Intra-observer agreement on the 'overall impression' was very good for Alzheimer's pattern (kappa=0.73-1.00), and fair to good for the 'heterogeneous pattern' (kappa=0.30-0.63). Inter-observer agreement, as reflected in per cent agreement, ranged from 29% to 100%. Inter-observer agreement about the 'overall impression' was fair to moderate for Alzheimer's pattern (kappa=0.24-0.54) and was poor for the descriptors 'heterogeneous' and 'normal'. It is concluded that brain SPECT has great potential value in many important conditions. This study demonstrates a need for further work in the areas of pattern definition and reduction of observer variation.

Adult↗

Relapse of TEL-AML1--positive acute lymphoblastic leukemia in childhood: a matched-pair analysis.

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL-negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 +/- 0.10 versus 0.38 +/- 0.10 (P =.09) and 0.82 +/- 0.09 versus 0.42 +/- 0.19 (P =.10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P <.001) but not of TEL-AML1 expression (P =.09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.

Adolescent↗

A review of the evidence for overlap among unexplained clinical conditions.

PURPOSE: Unexplained clinical conditions share features, including symptoms (fatigue, pain), disability out of proportion to physical examination findings, inconsistent demonstration of laboratory abnormalities, and an association with "stress" and psychosocial factors. This literature review examines the nature and extent of the overlap among these unexplained clinical conditions and the limitations of previous research. DATA SOURCES: English-language articles were identified by a search of the MEDLINE database from 1966 to January 2001 by using individual syndromes and their hallmark symptoms as search terms. STUDY SELECTION: Studies that assessed patients with at least one unexplained clinical condition and that included information on symptoms, overlap with other unexplained clinical conditions, or physiologic markers. Conditions examined were the chronic fatigue syndrome, fibromyalgia, the irritable bowel syndrome, multiple chemical sensitivity, temporomandibular disorder, tension headache, interstitial cystitis, and the postconcussion syndrome. DATA EXTRACTION: Information on authorship, patient and control groups, eligibility criteria, case definitions, study methods, and major findings. DATA SYNTHESIS: Many similarities were apparent in case definition and symptoms, and the proportion of patients with one unexplained clinical condition meeting criteria for a second unexplained condition was striking. Tender points on physical examination and decreased pain threshold and tolerance were the most frequent and consistent objective findings. A major shortcoming of all proposed explanatory models is their inability to account for the occurrence of unexplained clinical conditions in many affected patients. CONCLUSIONS: Overlap between unexplained clinical conditions is substantial. Most studies are limited by methodologic problems, such as case definition and the selection and recruitment of case-patients and controls.

Brain Concussion↗

Molecular quantification of response to therapy and remission status in TEL-AML1-positive childhood ALL by real-time reverse transcription polymerase chain reaction.

Although TEL-AML1 positivity [translocation t(12;21)(p13;q22)], detected in 20-25% of initial childhood acute lymphoblastic leukemia (ALL), has been associated with an excellent prognosis, its positive predictive value is insufficient for appropriate treatment stratification considering reported prevalence in relapsed ALL (3-28%). Molecular quantification of response to therapy by PCR-based methods has been shown to improve risk assessment. Here, we report on the sensitive quantification of leukemia-specific TEL-AML1 fusion transcript levels normalized to beta-actin expression (sensitivity threshholds, 10(-5)) by a novel real-time reverse transcription-PCR (RQ-RT-PCR) based on fluorescent TaqMan technique providing early and rapid evidence on the treatment efficacy of children with initial or relapsed TEL-AML1+ ALL enrolled in frontline or relapse trials of the Berlin-Frankfurt-Münster (BFM)-Study Group. In initial ALL, TEL-AML1/beta-actin decrease was > or =10(5)-fold in 50% of patients after induction therapy (day 33) and stayed TEL-AML1-negative throughout therapy, which suggested high sensitivity of leukemic cells to antineoplastic therapy. The remaining patients were still TEL-AML1+ before reintensification (ratios, 0.7 x 10(-2):10(-4)). In relapsed ALL, TEL-AML1/beta-actin decrease was generally less pronounced at corresponding time points, and conversion to TEL-AML1 negativity was observed in 40% of patients. Most notably, subsequent relapses occurred only among molecular poor responders, whereas all early responders remain in their second complete remission. In conclusion, real-time quantification of TEL-AML1/beta-actin kinetics distinguishes distinct molecular response groups, and provides indications capable of directing therapeutic interventions for patients with TEL-AML1+ ALL. Before considering modification of therapy, results should be interpreted cautiously taking into account the long duration of remission associated with TEL-AML1+ ALL.

Actins↗

Characterization of cytokine, growth factor receptor, costimulatory and adhesion molecule expression patterns of bone marrow blasts in relapsed childhood B cell precursor all.

Relapse of childhood acute lymphoblastic leukaemia (ALL) comprises a leading challenge of investigation. Characterization of leukaemic cells regarding their potency to express growth factors and surface molecules can provide insight into their aberrant biology. Thus, we analyzed bone marrow blasts from 10 children with relapsed B cell precursor ALL. The gene and protein expression of essential haematopoietic growth factors (IL-2, IL-4, IL-7, IL-10, IL-15, IFN-gamma, G-CSFR), their corresponding receptors as well as the expression pattern of adhesion molecules (ICAM-1, CD58) and costimulatory proteins (CD40, CD40L, B7.1, B7.2, CD28, MHC-I and II) was analyzed by RT-PCR and flow cytometry. Constitutive gene expression was found for IL-7, IL-10, IL-15 and IFN-gamma and their corresponding receptors. Flow-cytometric analysis showed that IL-10R, IL-7Ralpha, IL-4Ralpha and the gamma(c)chain are constitutively expressed, and that some cells bear the G-CSFR. IL-10 and IL-15 protein-producing leukaemic cells were easily detectable. The neoplastic cells mainly lack B7.1, and ICAM-1 is mostly decreased. Furthermore, high CD40, and, surprisingly, CD40L expression could be found. These studies show that ALL cells are likely to be sensitive to many growth factors and some factors are produced by the neoplastic cell itself. The secretion of IL-10 by leukaemic cells, and the absence or downregulation of conventional adhesion and costimulatory molecules might represent an effective mechanism of escape of immune surveillance in relapsed ALL.

Adolescent↗

Fibromyalgia and other unexplained clinical conditions.

Several unexplained clinical conditions frequently coexist with fibromyalgia; these include chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension and migraine headaches, and others. However, only recently have studies directly compared the physiological parameters of these conditions (eg, fibromyalgia vs irritable bowel syndrome) to elucidate underlying pathogenic mechanisms. This review summarizes data from comparative studies and discusses their implications for future research.

Colonic Diseases, Functional↗

Health-related quality of life in patients with chronic fatigue syndrome: an international study.

OBJECTIVE: Chronic fatigue syndrome (CFS) has been reported worldwide. Our objectives were to determine if patients from different countries have similar profiles of impairments. METHODS: Health-related quality of life (HRQoL) was assessed in 740 CFS patients in the US, 82 in the UK, and 65 in Germany using the eight subscales of the Short-Form General Health Survey (SF-36). To examine the internal structure, factor analyses were performed. RESULTS: Overall, there was a remarkable similarity in HRQoL among all CFS patients, regardless of location. Patients scored two to three standard deviations below normal on six subscales and one standard deviation below normal on the other two subscales. Factor analysis suggested a two-factor model where the same six subscales constitute the first factor and the two others the second factor. CONCLUSION: HRQoL is poor in CFS patients from three countries. This study is a first step towards conducting further comparative cross-cultural and international studies.

Adolescent↗

The impact of hypertension on the operative and early postoperative outcome of aortic valve surgery.

Hypertension is a known risk factor in heart disease. It can lead to pressure overload and hypertrophy of the left ventricle. The aim of this study is to examine the effect of hypertension on the operative and early postoperative outcome after aortic valve surgery using the retrograde cardioplegia. All the data of all the patients who had aortic valve surgery in our department were retrospectively examined during the period from January 1994 until April 1996 and received retrograde blood cardioplegia. 397 patients were included in this study. 213 of them had arterial hypertension, as preoperatively diagnosed by the referring cardiologist. There were 163 females and 234 males. 142 were above 70 yr of age. 22 patients had an ejection fraction (EF) < or =0.4 and in 168 patients the LVEDP was >15 mmHg. Hypertension alone proved to be no risk factor. Decreased EF in hypertensive patients leads to an increase in the occurrence of prolonged ICU-stay, low cardiac output and neurological complications. Hypertension alone does not increase the risk of operative and early postoperative aortic valve surgery.

Adolescent↗

Preventive care of older urban American Indians and Alaska natives in primary care.

Little is known about prevention among elderly or urban American Indian/Alaska Native (AI/AN) populations. We reviewed the medical records of 550 older urban AI/AN primary care patients to evaluate how frequently preventive measures were received. Adherence to guidelines was examined by a culturally appropriate (> or =50 years) and standard age threshold (> or =65 years), and by performance of preventive measures at any time ("ever") and in the past year. Lifetime performance was inadequate for the many measures, including mammograms (56%), fecal occult blood testing (37%), audiometry (33%), visual acuity testing (50%), smoking cessation counseling (50%), and pneumococcal (22%) and influenza (49%) vaccinations. Performance of the measures was less frequent in the prior year, but did not differ by age threshold. Predictors of adherence included female gender, having insurance, and having more health problems and medications. Nonadherence infrequently resulted from patients' failure to comply with recommendations. We conclude that use of most preventive services among elderly urban AI/ANs is suboptimal and should be improved.

Age Factors↗

Monozygotic twins discordant for chronic fatigue syndrome: regional cerebral blood flow SPECT.

PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS. MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m-hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors. RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging. CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.

Adult↗

The impact of normothermia on the outcome of aortic valve surgery.

The purpose of this study was to examine the effects of systemic perfusion temperature on the clinical outcome after aortic valve surgery. In this study, we examined 323 patients who underwent aortic valve surgery between January 1994 and April 1996. Forty-six patients were perfused in moderate hypothermia (28 degrees C) and 277 patients in normothermia. Age and sex distribution of the patients were similar. There were no statistically significant differences between the groups regarding neurological, renal or cardiac complications. Patients in hypothermia required less catecholamine at the end of the operation (p = 0.00001), but there was no significant difference in the length of the stay in the intensive care unit between the groups. Cardiopulmonary bypass temperature did not influence early outcome after aortic valve surgery.

Aortic Valve↗

Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact?

This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function. Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise. The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.

Adult↗

Decreased nocturnal levels of prolactin and growth hormone in women with fibromyalgia.

Fibromyalgia (FM) is a complex syndrome, primarily of women, characterized by chronic pain, fatigue, and sleep disturbance. Altered function of the somatotropic axis has been documented in patients with FM, but little is known about nocturnal levels of PRL. As part of a laboratory study of sleep patterns in FM, we measured the serum concentrations of GH and PRL hourly from 2000--0700 h in a sample of 25 women with FM (mean, 46.9 +/- 7.6 yr) and in 21 control women (mean, 42.6 +/- 8.1 yr). The mean (+/-SEM ) serum concentrations (micrograms per L) of GH and of PRL during the early sleep period were higher in control women than in patients with FM [GH, 1.6 +/- 0.4 vs. 0.6 +/- 0.2 (P < 0.05); PRL, 23.2 +/- 2.2 vs. 16.9 +/- 2.0 (P < 0.025)]. The mean serum concentrations of GH and PRL increased more after sleep onset in control women than in patients with FM [GH, 1.3 +/- 0.4 vs. 0.3 +/- 0.2 (P < 0.05); PRL, 16.2 +/- 2.4 vs. 9.7 +/- 1.5 (P < 0.025)]. Sleep efficiency and amounts of sleep or wake stages on the blood draw night were not different between groups. There was a modest inverse relationship between sleep latency and PRL and a direct relationship between sleep efficiency and PRL in FM. There was an inverse relationship between age and GH most evident in control women. Insulin-like growth factor I levels were not different between the groups. These data demonstrate altered functioning of both the somatotropic and lactotropic axes during sleep in FM and support the hypothesis that dysregulated neuroendocrine systems during sleep may play a role in the pathophysiology of FM.

Adult↗