Search PubMed⌕ Search

Biomedical subjects

D J Clauw

Publications and source records attributed to D J Clauw.

At least 37 records · Page 2Linked to original sources
PubMed1996

Animal models of the eosinophilia-myalgia syndrome.

Shortly after the recognition of the eosinophilia-myalgia syndrome (EMS), several investigators did studies to replicate the cardinal features of this disorder in animals. These studies originally involved administration of both L-tryptophan (LT) and of specific compounds that were found in higher concentrations in lots of LT linked to the development of disease. Several of these studies claimed to represent an animal model of EMS because they reproduced some features of the human disease. However, a critical review of all the animal studies casts doubt on the validity of these assertions. These studies could generally not be reproduced and had methodologic flaws that limited extrapolation of results. Although the epidemiologic studies suggest that most cases of EMS were linked to ingestion of LT from a single manufacturer, the aggregate animal data in this area neither confirm nor rule out this hypothesis. The precise cause of EMS remains unknown.

Animals↗
PubMed1995

Fibromyalgia: more than just a musculoskeletal disease.

Fibromyalgia is a common condition characterized by diffuse musculoskeletal pain and fatigue. The syndrome is defined by the presence of musculoskeletal tender points on physical examination. Additionally, persons with this syndrome have a high incidence of headaches, ocular and vestibular complaints, paresthesias, esophageal dysmotility, "allergic" symptoms, irritable bowl syndrome, genitourinary symptoms and affective disorders. Recent research has revealed a number of objective biochemical, hormonal and neurotransmitter abnormalities associated with fibromyalgia, making it a clearly identifiable condition. These abnormalities may clarify our understanding of the pathogenesis and treatment of fibromyalgia.

Diagnosis, Differential↗
PubMed1995

The eosinophilia-myalgia syndrome: status of 205 patients and results of treatment 2 years after onset.

OBJECTIVE: To describe the course of the eosinophilia-myalgia syndrome during a 2-year period. DESIGN: 15 physicians completed a structured review form to describe symptoms, physical findings, laboratory data, and responses to treatments in 205 patients with the eosinophilia-myalgia syndrome at the onset of illness and after 18 to 24 months of follow-up. SETTING: 15 university and private clinical practice settings. PATIENTS: 205 patients for whom follow-up data were available and who met four criteria at diagnosis: eosinophil count of 1000 cells/mm3 or greater; presence of fasciitis, peripheral neuropathy, polyradiculopathy, interstitial pulmonary disease, pulmonary hypertension, or myocardial involvement; history of L-tryptophan consumption; and absence of other conditions that could account for these findings. INTERVENTION: Empirical interventions by the physicians. MEASUREMENTS: Symptoms, physical findings, laboratory test results, biopsy findings, radiographic reports, therapeutic interventions, and responses to these interventions. RESULTS: After 18 to 24 months, all symptoms except cognitive changes were reported to have improved in most patients. Nearly all physical findings were also reported to have improved or resolved in most patients; only peripheral neuropathy was unchanged. No evidence of ongoing inflammatory disease was reported. Prednisone was reported to be helpful in 79% of patients who received it during the acute phase of the syndrome. No other treatment was reported to be consistently beneficial. CONCLUSIONS: 18 to 24 months after the onset of illness, most symptoms and physical findings in most patients with the eosinophilia-myalgia syndrome resolved or improved. Cognitive changes were reported to be worse in 32% of patients. Prednisone was helpful in the acute phase of illness. No treatment was clearly valuable in management of the later phase of the syndrome.

Adult↗
PubMed1995

The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia.

Syndromes characterized by chronic pain and fatigue have been described in the medical literature for centuries. Fibromyalgia is the term currently used to describe this symptom complex, and considerable research has been performed in the last decade to delineate the epidemiology, pathophysiology, and genesis of this entity. Although fibromyalgia is defined by its musculoskeletal features, it is clear that there are a large number of non-musculoskeletal symptoms, such that we now understand that there is considerable overlap with allied conditions such as the chronic fatigue syndrome, migraine and tension headaches, irritable bowel syndrome, and affective disorders. This article will review our current state of knowledge regarding fibromyalgia and these allied conditions, and present a unifying hypothesis that describes both the pathophysiology of symptoms and the genesis of these disorders.

Autonomic Nervous System↗
PubMed1995

Eosinophilic rheumatic disorders.

Almost any rheumatic disorder can occasionally be characterized by the presence of eosinophilia, but there are only a few in which eosinophilia is a defining characteristic. These include eosinophilic fasciitis as well as toxin-induced disorders such as eosinophilia-myalgia syndrome and toxic oil syndrome. The epidemiology, clinical features, and pathogenesis of these conditions are reviewed in this article, and a rational approach to management of these entities is discussed.

Diagnosis, Differential↗
PubMed1994

Magnesium deficiency in the eosinophilia-myalgia syndrome. Report of clinical and biochemical improvement with repletion.

We describe a patient with the eosinophilia-myalgia syndrome (EMS) with persistent myalgias, cramping, and weakness that were not responsive to treatment. Despite a normal serum magnesium level, a loading study was performed, and the results suggested low tissue levels of magnesium. He was given parenteral magnesium and had dramatic improvement in symptoms as well as in muscle intracellular levels of this cation. After cessation of magnesium therapy the symptoms recurred, and magnesium repletion again led to an improvement in symptoms and ATP levels. Low tissue levels of magnesium, even in the setting of normal serum levels, may lead to the neuromuscular symptoms in EMS and related disorders.

Adenosine Triphosphate↗
PubMed1994

Pharmacogenetic characteristics of the eosinophilia-myalgia syndrome.

This study tested the hypothesis that patterns of xenobiotic metabolism in patients with eosinophilia-myalgia syndrome (EMS) differed from healthy control subjects. We determined the genotypes of 27 EMS patients with EMS and 114 control subjects for the cytochrome P450 CYP2D6 polymorphism. The metabolic phenotypes of patients with EMS for S-mephenytoin hydroxylation (n = 17) and dapsone acetylation (n = 19) were determined and compared with 29 healthy control subjects. The incidence of the CYP2D6 poor metabolizer genotype (mutant/mutant) was 0.185 in patients with EMS and 0.061 in control subjects (Mantel-Haenszel, chi 2 = 7.213, p = 0.007). The mephenytoin S/R ratios were 0.39 +/- 0.23 in patients with EMS versus 0.18 +/- 0.13 in control subjects (p < or = 0.005). There was no difference in dapsone acetylation between the two groups. A pattern of xenobiotic metabolism may play a role in the pathogenesis of EMS, but the precise role that it plays remains unclear.

Alleles↗
PubMed1994

Eosinophilia-myalgia syndrome not associated with the ingestion of nutritional supplements.

The eosinophilia-myalgia syndrome (EMS) is a recently recognized illness characterized by peripheral eosinophilia, myalgias, and a variety of neurologic, cutaneous, and pulmonary features. Most of those afflicted with this disorder consumed L-tryptophan, but some cases have occurred in association with the ingestion of other nutritional supplements. We describe someone who developed EMS in 1986 without the ingestion of any nutritional supplements. He was also found to have slowed P450 metabolism, in a pattern seen in other patients with EMS. We postulate that EMS can occur in association with the ingestion of multiple substances that share minute quantities of a common, as yet unidentified, toxin(s), and that metabolic host factors may contribute to disease susceptibility.

Adult↗
PubMed1994

P-31 magnetic resonance spectroscopy of skeletal muscle in the eosinophilia-myalgia syndrome: a preliminary study.

OBJECTIVE: To determine the pathogenesis of muscular symptomatology in the eosinophilia-myalgia syndrome (EMS). METHODS: P31-nuclear magnetic resonance spectroscopy (MRS) was performed on 7 patients with EMS and 10 age matched controls to determine the relative concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), and adenosine triphosphate (ATP) in calf muscle. RESULTS: Patients with EMS had statistically lower ATP/PCr ratios and higher Pi/ATP ratios than controls, indicating a preferential and unique decrease in ATP levels at rest in skeletal muscle. CONCLUSION: Skeletal muscle is metabolically abnormal in patients with EMS. This abnormality may contribute to the myalgia, spasm, and weakness seen in this disorder.

Adenosine Triphosphate↗
PubMed1990

Tryptophan-associated eosinophilic connective-tissue disease. A new clinical entity?

Seven patients who developed a syndrome of eosinophilia, connective-tissue disease, and cutaneous abnormalities while ingesting tryptophan were examined. Other clinical manifestations commonly seen were pulmonary symptoms, fever, lymphadenopathy, and the development of myopathy. Laboratory features included mild elevations of aldolase and lactate dehydrogenase levels, with essentially normal creatine kinase levels, erythrocyte sedimentation rates, and C-reactive protein levels. Biopsy findings included features of scleroderma, small-vessel vasculitis, fasciitis, and myopathy. Discontinuation of tryptophan administration and implementation of corticosteroid therapy were of some benefit in relieving the intense myalgias and cutaneous findings that developed. Although temporally related to tryptophan ingestion, it is unclear whether this substance, a metabolite, or a contaminant were causal. We speculate that the pathogenesis of this syndrome may relate to abnormalities in tryptophan metabolism.

Adult↗
PubMed1983

The cytokinetic and cytotoxic effects of ICRF-159 and ICRF-187 in vitro and ICRF-187 in human bone marrow in vivo.

The cytotoxic and cytokinetic effects of ICRF-159 and its d-enantiomer ICRF-187 have been examined in vitro. The effects of both agents were identical. Cytotoxicity is dependent on both the drug concentration and the duration of drug exposure. Drug exposure for twice the cell cycle time is necessary for maximum effect. Cytotoxicity is also dependent upon the rate of cell proliferation. A rapidly growing cell population is more sensitive to brief drug exposure than a slowly growing population. The cytokinetic effects were studied using flow cytometry, determination of [3H]-thymidine incorporation and mitotic index. ICRF-159/187 appears to act only during the G2 phase of the cell cycle. There is no detectable delay in cell passage through the G1/S boundary or in transit through S phase. Inhibition of DNA synthesis occurs only after the G2 block prevents subsequent entry of cells in S phase. A fraction of the cells, depending upon drug concentration, undergo further DNA synthesis without cell division, resulting in a tetrapoid cell population. The cytokinetic effects were determined in the bone marrow of patients receiving ICRF-187. All dose-rates produced G2/M accumulation in the marrow with depletion of S phase cells. One patient was given a single injection of 1.0 gm/M2 . G2/M accumulation was observed 24 h after treatment, with recovery to a pretreatment DNA cycle distribution 24 h later. These studies suggest that a continuous drug infusion, or intermittent infusions timed to allow the normal cell population to recover, may produce superior clinical activity with this agent. A Phase I study of such an intermittent schedule is indicated.

Antineoplastic Agents↗
PubMed1982

Cytokinetic evaluation of the four-drug combination of bleomycin, vincristine, mitomycin C, and methotrexate (BOMM) in cultured Burkitt's lymphoma cells and human bone marrow.

The four-drug combination of bleomycin, vincristine, mitomycin C and methotrexate produces a high response rate in patients with squamous cell carcinoma. In this study we have examined the cytokinetic effects of this drug combination in vitro and in human bone marrow in vivo. The in vitro analysis revealed that mitomycin C produces a concentration dependent slowing of S-phase transit with partial G2/M and G1/S blocks in cell cycle progression. A partially synchronized S-wave occurs 4-8 and 16-20 hours following a two-hour drug exposure. Bleomycin produces a dose dependent G2/M block during a 14-hour drug exposure. Drug removal did not result in appreciable cell cycle synchrony. In vitro exposure to the two drug combination resulted in loss of both the marked G2/M accumulation seen with bleomycin, and the partially synchronized S-phase waves seen following mitomycin C exposure. The sequential changes in bone marrow cytokinetics were determined in eight patients during and following administration of vincristine, mitomycin C and a continuous four-day infusion of bleomycin. The major cytokinetic changes observed were an increase in G2/M phase cells 18 hours following vincristine, and an increase in thymidine incorporation and S-phase cells 24 and 48 hours following the end of the bleomycin infusion. The clinical course of 24 patients was reviewed. Eleven patients who received methotrexate 36 to 42 hours following bleomycin had a subsequent median leukocyte nadir of 1.8 x 10(3)/mm3. Thirteen patients receiving methotrexate 60 to 72 hours after bleomycin had median leukocyte nadir of 3.9 x 10(3)/mm3. The objective response rates in the two groups was 75% and 80%, respectively. This study demonstrates that bone marrow cytokinetic analysis may allow schedule modification to avoid myelosuppression without loss of therapeutic activity.

Antineoplastic Agents↗
PubMedDate not supplied

The relationship between fibromyalgia and interstitial cystitis.

Interstitial cystitis (IC) is a relatively uncommon and enigmatic disorder characterized by pain in the bladder and pelvic region, typically accompanied by urinary urgency and frequency. Fibromyalgia is a more common disorder, with the prominent symptoms being diffuse musculoskeletal pain and fatigue, and it has been well established that there is substantial clinical overlap between fibromyalgia and chronic fatigue syndrome (CFS). Although genitourinary and musculoskeletal symptoms predominate in IC and fibromyalgia respectively, both disorders share a number of features, including similar demographics, "allied conditions" (e.g. irritable bowel syndrome, headaches, etc.), natural history, aggravating factors, and efficacious therapy. We hypothesized that there was substantial clinical overlap between fibromyalgia and IC, and examined cohorts of individuals with these two disorders in parallel, to compare the spectrum of symptomatology. Sixty fibromyalgia patients, 30 IC patients, and 30 age-matched healthy controls were questioned regarding current symptomatology. A dolorimeter examination was also performed in the three groups to assess peripheral nociception. We found that the frequency of current symptoms was very similar for the fibromyalgia and IC groups. Both the fibromyalgia and IC patients displayed increased pain sensitivity when compared to healthy individuals, at both tender and control points. These data suggest that IC and fibromyalgia have significant overlap in symptomatology, and that IC patients display diffusely increased peripheral nociception, as is seen in fibromyalgia. Although central mechanisms have been suspected to contribute to the pathogenesis of fibromyalgia for some time, we speculate that these same types of mechanisms may be operative in IC, which has traditionally been felt to be a bladder disorder.

Adult↗
PubMedDate not supplied

Psychiatric aspects of the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS) is a rare systemic disease caused by presumably contaminated L-tryptophan. Thirteen outpatients with EMS were found to have a high degree of depression, anxiety, and difficulty adjusting to illness. Pre-EMS history of major depression but not EMS severity predicted poor adjustment to illness.

Adaptation, Psychological↗
PubMedDate not supplied

Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause. This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses.

Central Nervous System↗