RESUMO
BACKGROUND: The utility of measuring histamine and prostaglandin metabolites in the urine of patients with mastocytosis has not been critically examined in a large series of patients. This study examined the relationship between the extent of increase in urinary excretion of 11ß-prostaglandinF2α and N-methyl histamine, with serum tryptase, whole blood serotonin, and bone marrow findings including morphology, percentage involvement, and abnormal mast cell phenotype. METHODS: This was a retrospective analysis of 90 patients who were continuously enrolled in the study for a period of 6 years (2008-2014). We recorded serum tryptase, whole blood serotonin, levels of urinary mast cell metabolites 11ß-prostaglandinF2α and N-methyl histamine (NMH), and bone marrow findings. RESULTS: Urinary mast cell metabolites 11ß-prostaglandinF2α and N-methyl histamine correlated with levels of serum tryptase, mast cell burden in the bone marrow, the presence of mast cell aggregates, and atypical mast cells on bone marrow biopsy. Whole blood serotonin did not have a significant correlation with the serum tryptase or mast cell burden in the bone marrow. Urinary NMH was significantly different between c-kit D816V-positive and c-kit D816V-negative patients, while 11ß-prostaglandinF2α was not. Urinary 11ß-prostaglandinF2α 24-h excretion >3500 ng and NMH levels >400 µg/gm Cr corresponded with the high degree of bone marrow biopsies positive for atypical mast cells, the presence of aggregates, and c-kit mutation. CONCLUSIONS: Easily obtained and quantified urinary metabolites of histamine (greater than twice the upper limit of normal) and prostaglandin D2 (>3.4 times the upper limit of normal) correlate well with bone marrow findings of mastocytosis.
Assuntos
Medula Óssea/patologia , Dinoprosta/urina , Mastocitose/patologia , Mastocitose/urina , Metilistaminas/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Criança , Feminino , Humanos , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , Mastocitose/sangue , Mastocitose/genética , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Serotonina/sangue , Triptases/sangue , Adulto JovemRESUMO
OBJECTIVES: Systemic mastocytosis (SM) is a disorder characterized by the excessive accumulation of clonally derived mast cells in various tissues. When triggered, mast cells release large amounts of histamine, prostaglandins and leukotrienes. Leukotriene E4 (LTE4) is the primary stable metabolite of total cysteinyl leukotrienes. We hypothesized that secretion of LTE4 would be increased in SM and could be used alone or in combination with current urinary biomarkers to optimize screening for SM. DESIGN AND METHODS: LTE4 was measured by liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). Analytical assay validation was performed using residual urine specimens. LTE4 results were normalized to urine creatinine for clinical use. Reference interval was established using a healthy volunteer cohort. Clinical sensitivity and specificity for SM detection were determined by measuring urinary biomarkers (LTE4, N-methyl histamine [NMH] and 11ß-prostaglandin F2α [BPG]) in a cohort of 409 patients referred to allergy specialists, 66 (16%) of which were diagnosed with SM. RESULTS: Urinary LTE4 measurement was accurate, precise and linear across a range of 31-3020pg/mL. The 95th percentile of the reference interval population was <104pg/mg creatinine. Median urine LTE4 concentrations were significantly higher among patients with SM (97pg/mg cr. vs. 50pg/mg cr.; p<0.01). Elevated urinary LTE4 was 48% sensitive and 84% specific for SM. Clinical sensitivity was 53% for BPG (>1000ng/mL) and 71% for NMH (>200ng/mL). Incorporating all three urinary metabolites improved the SM diagnostic sensitivity to 97%, with minimal change in specificity. CONCLUSIONS: We have developed a sensitive and precise LC-MS/MS assay for quantitation of LTE4 in urine. Incorporating LTE4 into a panel including BPG and NMH provides a much-needed screening tool for a complicated disease with non-specific symptoms and invasive confirmatory testing.
Assuntos
Biomarcadores/urina , Cromatografia Líquida/métodos , Leucotrieno E4/urina , Mastocitose/urina , Espectrometria de Massas em Tandem/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The disease extent of mastocytosis can be assessed by measurement of mediators or their metabolites, secreted from mast cells. In the present study, we compared results of urinary N-methylhistamine measurements with analysis of total tryptase in serum from patients with suspected mastocytosis. METHODS: Tryptase in serum was determined with the UniCAP tryptase fluor-enzyme-immunoassay, according to the manufacturers' instructions (Pharmacia, Woerden, Netherlands). N-methylhistamine in urine was determined by competitive radioimmunoassay, according to the manufacturers' instructions (Pharmacia). RESULTS: A significant correlation between serum tryptase and urine N-methylhistamine was found both for 138 patients aged 14 or older (Spearman Rank r(s)=0.43, p<0.0001) and for 23 younger patients (Spearman Rank r(s)=0.46, p=0.0267). The between-run coefficient of variation of the tryptase assay was half (6.7%) of the one (13%) found with the urinary N-methylhistamine assay. Both for urine N-methylhistamine and serum tryptase, a significant difference was found between corresponding biopsies with an increased number of mast cell aggregates and biopsies without such an increase. The difference between tryptase levels however was stronger (Mann-Whitney: p=0.0012) than the difference between N-methylhistamine levels (Mann-Whitney: p=0.0140). CONCLUSION: Serum tryptase discriminates better than urinary N-methylhistamine between patients with an increased number of mast cell aggregates and persons without such an increase.
Assuntos
Mastocitose/sangue , Mastocitose/urina , Metilistaminas/urina , Serina Endopeptidases/sangue , Humanos , Reprodutibilidade dos Testes , TriptasesRESUMO
Symptoms of mastocytosis have been attributed to the overproduction of both histamine and prostaglandin (PG) D2. Recently, we developed an assay for the major urinary metabolite of PGD2 (PGD-M), 9 alpha,11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid, and demonstrated that urinary excretion of this compound is markedly increased in patients with mastocytosis. It had been shown previously that measurement of the urinary excretion of histamine metabolites provides a more sensitive biochemical diagnostic indicator of systemic mastocytosis than does measurement of unmetabolized histamine. Therefore, we examined the correlation between the urinary excretion of the histamine metabolite, NT-methylhistamine, and PGD-M in urine samples from patients with mastocytosis. Urinary excretion of NT-methylhistamine and PGD-M was measured in 46 urine samples from 17 patients with histologically documented mastocytosis. Both compounds were quantified by mass spectrometry. In all urine collections showing an increase above normal (2 SD above the mean) in the excretion of NT-methylhistamine, the fold increase above normal in the urinary excretion of PGD-M was substantially greater. Further, in some urine samples from four patients whose excretion of NT-methylhistamine was consistently normal, the excretion of PGD-M was increased above normal by as much as 300%. These data indicate that quantification of the urinary excretion of PGD-M is a more sensitive biochemical diagnostic indicator of mastocytosis than is the quantification of NT-methylhistamine.
Assuntos
Mastocitose/diagnóstico , Prostaglandinas D/urina , Adulto , Creatinina/urina , Feminino , Histamina/análogos & derivados , Histamina/urina , Humanos , Masculino , Mastocitose/urina , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Aspirin therapy for patients with systemic mast cell disease (SMCD) decreases the production of prostaglandin D2, which is thought to be a major mediator of flushing. Paradoxically, in 5 to 10% of patients with SMCD, administration of aspirin causes massive mediator release and an anaphylactoid reaction. We attempted aspirin desensitization in a 34-year-old man with SMCD (confirmed by bone marrow biopsy) who was incapacitated by severe flushing episodes and hypotension. His baseline mediator levels of plasma calcitonin, urinary histamine, and urinary N-methyl-imidazoleacetic acid were abnormal. Pentagastrin stimulation increased the plasma level of calcitonin from 47 pg/mL to 130 pg/mL (normal, less than or equal to 110) at 5 minutes. Oral aspirin desensitization was begun; however, after a cumulative dose of 620 mg, an anaphylactoid reaction ensued in conjunction with hypotension, abdominal cramping, and flushing. Coincidentally, 1 hour after the episode, the plasma calcitonin level increased from 37 pg/mL to 540 pg/mL, and the serum tryptase level increased from 1 ng/mL to 3.9 ng/mL. Six hours after the episode, the urine level of histamine increased from 90 micrograms/g creatinine to 337 micrograms/g creatinine, and the urinary N-methylimidazoleacetic acid increased from 32 mg/24 h to 81 mg/24 h. Hence, the patient had increased basal levels of plasma calcitonin that increased substantially during aspirin desensitization and increased to above the upper limit of normal during pentagastrin stimulation. Human mast cells may be capable of producing calcitonin or causing secretion of calcitonin in response to skeletal changes.
Assuntos
Anafilaxia/induzido quimicamente , Aspirina/efeitos adversos , Calcitonina/sangue , Mastocitose/sangue , Adulto , Aspirina/administração & dosagem , Creatinina/urina , Dessensibilização Imunológica , Histamina/urina , Humanos , Imidazóis/urina , Masculino , Mastocitose/tratamento farmacológico , Mastocitose/urina , PentagastrinaRESUMO
The urinary glycosaminoglycans (uGAG) in eight patients (four adults and four children) with mastocytosis and eleven healthy subjects (five adults and six children) were examined for evidence of heparin and chondroitin sulfate E. The excretion of uGAG to urinary creatinine (uCr) in these patients was found to be 10.36 micrograms/mg for the children and 0.98 micrograms/mg for the adults, neither significantly different from healthy controls (p greater than 0.2). The uGAG was found to have a molecular mass between 10 kDa and 60 kDa by high performance liquid chromatography (HPLC). The content of the uGAG was found to consist of chondroitin sulfates without any evidence of heparin as assessed by specific chondroitinase ABC susceptibility. Disaccharide analysis following chondroitinase ABC digestion by HPLC Partisil-10 Pac separation revealed no evidence of chondroitin sulfate E and no differences in relative distribution of 0-, 4-, and 6-sulfated disaccharides between patients and healthy controls.
Assuntos
Glicosaminoglicanos/urina , Mastocitose/urina , Adulto , Envelhecimento/urina , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Humanos , Lactente , Valores de ReferênciaRESUMO
The carcinoid syndrome and its clinical manifestations have been discussed. The standard laboratory test for making that diagnosis is urinary 5-HIAA levels but newer, more sensitive tests may also be available.
Assuntos
Angioedema/diagnóstico , Glucagonoma/diagnóstico , Síndrome do Carcinoide Maligno/diagnóstico , Mastocitose/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Paniculite/diagnóstico , Sarcoidose/diagnóstico , Dermatopatias/diagnóstico , Angioedema/sangue , Proteínas Inativadoras do Complemento 1/análise , Eritema/etiologia , Glucagon/sangue , Glucagonoma/sangue , Glucagonoma/complicações , Histamina/urina , Humanos , Ácido Hidroxi-Indolacético/urina , Síndrome do Carcinoide Maligno/urina , Mastocitose/urina , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/complicações , Paniculite/sangue , Peptidil Dipeptidase A/sangue , Sarcoidose/sangue , Dermatopatias/sangue , Dermatopatias/etiologia , Síndrome , Deficiência de alfa 1-AntitripsinaRESUMO
A 45-year-old patient is described presenting with severe axial osteoporosis. The presence of maculopapular skin lesions and the combination of osteolytic and osteoblastic bone lesions led to the tentative diagnosis of systemic mastocytosis. This diagnosis was confirmed by measurement of urinary histamine metabolites and by bone biopsy showing increased numbers of mast cells and fibroblast-like cells. The importance of these diagnostic procedures in this rare cause of osteoporosis is discussed.
Assuntos
Mastocitose/complicações , Osteoporose/etiologia , Vértebra Cervical Áxis/patologia , Biópsia , Histamina/urina , Humanos , Imidazóis/urina , Masculino , Mastocitose/diagnóstico , Mastocitose/urina , Metilistaminas/urina , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Mast cell activation syndrome (MCAS) describes patients with episodes of mast cell mediator release, with negative bone marrow biopsy results, and the failure to meet the criteria for systemic mastocytosis. OBJECTIVE: Identify elevation of mast cell mediators of patients with MCAS. METHODS: We performed a retrospective study of 25 patients with MCAS who were evaluated at Mayo Clinic from 2006 to 2012. Patients were reviewed for MCAS symptoms and mast cell mediators, including serum tryptase and 24-hour urine N-methyl histamine (N-MH) and 11ß-prostaglandin-F2α (11ß-PGF2α). The study was approved by the institutional review board. RESULTS: Urinary 11ß-PGF2α was the most frequently elevated product in MCAS of our 25-patient cohort. Flushing and pruritus had the greatest correlation with elevation of 24-hour urine 11ß-PGF2α value at baseline. The serum tryptase level was elevated in 10 patients, whereas the N-MH level was elevated with 2 patients. Eight of 9 patients with MCAS and with elevated 24-hour urine 11ß-PGF2α who underwent aspirin therapy and follow-up urinary studies had normalization of this mediator (1 patient did not have a follow-up urine study). Six of these 9 patients with MCAS who underwent aspirin therapy had symptomatic improvement. CONCLUSION: We recommend measurement of 24-hour urine 11ß-PGF2α and serum tryptase levels of patients with symptoms suggestive of MCAS. Measurement of 24-hour urine 11ß-PGF2α and serum tryptase levels can help avoid misdiagnosis and overinterpretation of MCAS symptoms in clinical practice. Given that an elevation of 24-hour urine N-MH level was found only in 2 patients, measurement of this mediator may be less helpful in diagnosing MCAS. We recommend aspirin therapy for patients with MCAS and with elevated 24-hour urine 11ß-PGF2α levels.
Assuntos
Degranulação Celular , Dinoprosta/urina , Mastócitos/enzimologia , Mastocitose/diagnóstico , Triptases/sangue , Adulto , Idoso , Aspirina/uso terapêutico , Biomarcadores/sangue , Biomarcadores/urina , Degranulação Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/uso terapêutico , Feminino , Testes Hematológicos , Humanos , Masculino , Mastócitos/efeitos dos fármacos , Mastocitose/sangue , Mastocitose/tratamento farmacológico , Mastocitose/urina , Pessoa de Meia-Idade , Minnesota , Valor Preditivo dos Testes , Estudos Retrospectivos , Síndrome , Resultado do Tratamento , Urinálise , Adulto JovemRESUMO
To study the long-term histamine turnover in patients with mastocytosis, the urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid was measured. Eighteen patients, 10 with urticaria pigmentosa and 8 with systemic mastocytosis, were followed for several years (mean 4.2 years). Younger individuals (less than 30 years) had initially normal excretion or tended to normalize their excretion during follow-up, while older patients (greater than 30 years) often had systemic manifestations and higher excretion values, which increased in some cases during the observation period.
Assuntos
Histamina/metabolismo , Mastocitose/metabolismo , Adolescente , Adulto , Idoso , Criança , Humanos , Imidazóis/urina , Mastocitose/urina , Pessoa de Meia-IdadeRESUMO
The symptoms and hemodynamic alterations that accompany systemic mast cell activation have been attributed in large part to an excessive release of prostaglandin D2 (PGD2). Further, PGD2 has been implicated in the adverse effects of some pharmacologic agents (e.g. nicotinic acid). Quantitation of the major urinary metabolite of PGD2 has been invaluable in elucidating a role for PGD2 in these clinical entities and in the biochemical diagnosis of the disease systemic mastocytosis. However, the stable-isotope mass spectrometric assay originally developed for quantification of this metabolite has been too cumbersome for routine use. We now report improvements in the assay that greatly increase its utility by shortening sample processing and eliminating the need for purification using thin-layer chromatography. The precision and accuracy of the modified assay was evaluated and found to be comparable with the previously described assay. These modifications potentially allow wider use of the assay to explore the role of PGD2 in human disease and in the routine biochemical diagnosis of systemic mastocytosis and other disorders of mast cell activation.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Prostaglandinas D/urina , Feminino , Humanos , Masculino , Mastocitose/diagnóstico , Mastocitose/urina , Reprodutibilidade dos TestesRESUMO
Treatment of four mastocytosis patients with the mast cell stabilising drugs, disodium cromoglycate and ketotifen failed to alter significantly the urinary excretion levels of histamine or N tau-methylimidazole acetic acid. No clinical improvement was noted in any subject after treatment by either drug.
Assuntos
Cromolina Sódica/uso terapêutico , Histamina/urina , Imidazóis/urina , Cetotifeno/uso terapêutico , Mastocitose/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Mastocitose/urina , Pessoa de Meia-IdadeRESUMO
A newly developed radioimmunoassay (RIA, Y) for the determination of urinary N tau-methylhistamine concentrations was correlated with gas chromatography mass spectrometry (GCMS, X). In 34 urine samples, with histamine and N tau-methylhistamine levels within our reference values, the correlation was: Y = 1.47X -0.245 mumol/l (r = 0.92; p-slope less than or equal to 0.0001). In 14 pathological urine samples, derived from patients with mastocytosis and having upper reference values, the correlation was: Y = 1.75X - 1.02 mumol/l (r = 0.93; p-slope less than or equal to 0.001). In spite of the greater specificity of the monoclonal antibody for N tau-methylhistamine compared with that of histamine, relatively high urinary histamine concentrations gave a false positive influence on the RIA results, which was 100% when the histamine/N tau-methylhistamine ratio was about 19. Clear cases of mastocytosis can be diagnosed, using the RIA-kit, but for a more precise N tau-methylhistamine value GCMS analyses will remain necessary.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Mastocitose/urina , Metilistaminas/urina , Radioimunoensaio , Reações Falso-Positivas , Cromatografia Gasosa-Espectrometria de Massas/estatística & dados numéricos , Humanos , Radioimunoensaio/estatística & dados numéricos , Valores de ReferênciaRESUMO
The determination of the metabolites of histamine, 1-methylhistamine (MHIS) and 1-methylimidazoleacetic acid (MIIA), in human urine is a useful tool for the diagnosis of mastocytosis. MHIS was extracted under basic conditions with chloroform and derivatized with trifluoroacetic acid anhydride, MIIA was derivatized with pentafluorobenzylbromide prior to extraction under basic conditions and the derivative was extracted with chloroform. The samples were assayed by gas chromatography-mass spectrometry. Normal concentrations of MHIS (2.01 micromol l(-1)) and MIIA (21.3 micromol l(-1)) in healthy volunteers' urine samples are clearly detectable with coefficients of variation of 7.0 and 8.9%. Pathological concentrations of 10.1 and 113 micromol l(-1) for MHIS and MIIA, respectively, are quantifiable with coefficients of variation of 6.6 and 4.8%.
Assuntos
Imidazóis/urina , Mastocitose/diagnóstico , Metilistaminas/urina , Calibragem , Estudos de Casos e Controles , Cromatografia Gasosa , Humanos , Espectrometria de Massas , Mastocitose/urina , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To evaluate the natural course of indolent mastocytosis in adults. DESIGN: A retrospective long-term follow-up study. SETTING: The Department of Endocrinology of a University Hospital. PATIENTS: Sixteen adult patients with a diagnosis of indolent mastocytosis and sufficient biochemical data for statistical analysis. One patient had paediatric-onset cutaneous mastocytosis, whilst the others had adult-onset systemic mastocytosis. Ages at the end of follow-up ranged from 23 to 79, median 50 years. Follow-up periods per patient lasted from 13 to 135 months, median 90 months. MEASUREMENTS: Urinary excretions of the histamine metabolites N tau-methylhistamine (MH) and N tau-methylimidazoleacetic acid (MIMA), and signs and symptoms of the disease. RESULTS: The excretion of MH but not MIMA increased in four patients (ages 37, 45, 61 and 65 years) and decreased in two patients (ages 26 and 48 years), including the only patient with paediatric-onset cutaneous mastocytosis. The excretion of MIMA but not MH increased in none and decreased in one patients (age 51 years). The excretions of both MH and MIMA increased in one patient (age 23 years) and decreased in two patients (ages 65 and 79 years). The excretion of MH and MIMA can be considered to have been stable in one patient (age 49 years). In the five remaining patients, observation periods were rather short. A definite judgement on the course of their disease could not be given. In the two patients in whom the excretion of both MH and MIMA decreased, the enlarged spleen decreased in size, whilst in the other patients, signs and symptoms did not change. There were no accompanying myeloproliferative disorders in any patient. No special treatment aiming at a reduction in mast cell load has been given. Rates of change over the whole follow-up period ranged from -8.4 to +25.1% per year. CONCLUSION: The natural course of indolent adult-onset mastocytosis is not always progressive. Our data show that the activity of adult-onset indolent mastocytosis, as measured by urinary excretion of MH and MIMA and clinical signs and symptoms, can substantially decline, especially in older patients.
Assuntos
Imidazóis/urina , Mastocitose/urina , Metilistaminas/urina , Adulto , Idoso , Doenças da Medula Óssea/urina , Feminino , Seguimentos , Humanos , Hepatopatias/urina , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esplenopatias/urinaRESUMO
Thirty-seven patients with mastocytosis and unexplained elevated levels of urinary N-methylhistamine who were undergoing bone marrow biopsy were studied with respect to the diagnosis of mastocytosis and the manifestations of the disease. These patients were from a group of 66 patients from whom a bone marrow biopsy was obtained and urinary N-methylhistamine levels were measured in the period 1990-1998. In seven (19%) of the 37 patients, mastocytosis was limited to the skin. Five (14%) of the 37 patients showed accumulation of mast cells in the bone marrow without characteristic skin lesions, whereas seven (19%) of the 37 patients showed increased numbers of mast cells both in the skin and the bone marrow. Eighteen (49%) of the 37 patients with elevated N-methylhistamine did not have mast cell accumulation in either the skin or the bone marrow biopsy. The median level of N-methylhistamine in the urine of patients with mastocytosis limited to the skin was 245 micro mol/mol creatinine. The average level of N-methylhistamine was 509 micro mol/mol creatinine in patients with mast cell accumulation in the bone marrow and cutaneous mastocytosis. There was a significant difference in the levels of N-methylhistamine in patients with mast cell accumulation in the bone marrow biopsy compared with those without. The likelihood of mastocytosis with mast cell accumulation in the bone marrow biopsy at a given level of N-methylhistamine was calculated. It was established that an N-methylhistamine level of 297 micro mol/mol creatinine or higher may be considered as a threshold indicator for obtaining a bone marrow biopsy in patients suspected of mastocytosis with mast cell accumulation in the bone marrow. For practical purposes, we propose to consider the cut-off level of approximately 300 micro mol/mol N-methylhistamine creatinine for this assay.
Assuntos
Medula Óssea/patologia , Mastocitose/patologia , Metilistaminas/urina , Biomarcadores/urina , Biópsia , Humanos , Mastócitos/patologia , Mastocitose/urina , Curva ROC , Sensibilidade e Especificidade , Pele/patologiaRESUMO
Urine eosinophil cationic protein (U-ECP), blood eosinophils and eosinophils in bladder biopsy specimens were studied in 30 patients with painful bladder disease (15 with detrusor mastocytosis, i.e. interstitial cystitis (IC) (greater than or equal to 28 mast cells/mm2 in the detrusor muscle) and 15 patients without detrusor mastocytosis). In patients with IC the median concentration of U-ECP was 140 arbitrary u/l versus 14 arb. u/l in the remaining patients (P less than 0.001). The mean peripheral leukocyte count was significantly lower in the IC group (P less than 0.05). Tissue infiltration with eosinophils was found in 43% of the bladder biopsies from patients with IC compared with 4% of the biopsies in the remaining patients (P less than 0.05). A negative correlation between peripheral eosinophils and U-ECP was found in the patients with IC (r = 0.52, P less than 0.05). These results suggest that eosinophils are attracted to the inflammatory site in the bladder wall where ECP is released. Eosinophils thus seem to participate actively in the inflammatory process. U-ECP seems to provide valuable diagnostic information when diagnosing IC in patients with painful bladder disease. It is suggested that ECP might be involved in the process of tissue destruction in IC.
Assuntos
Proteínas Sanguíneas/análise , Cistite/urina , Mastocitose/urina , Ribonucleases , Adulto , Idoso , Cistite/patologia , Proteínas Granulares de Eosinófilos , Eosinófilos/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Contagem de Leucócitos , Mastocitose/patologia , Pessoa de Meia-Idade , Bexiga Urinária/patologiaRESUMO
Six patients with documented systemic mast cell disease were enrolled in a 1-year, phase I study to determine the possible benefits of interferon alpha-2b (IFN-alpha). IFN-alpha therapy was begun at a dosage of 0.5 million units/day (MU/day) by subcutaneous injection and increased, as tolerated, to 3.0 MU/day. Subsequent dose modifications were made based on clinical tolerance and response. No immediate, adverse reactions to IFN-alpha occurred. Several patients showed symptomatic improvement. In two patients ascites resolved and did not recur. Two other patients reported improved energy levels and had decreased size of retroperitoneal, measenteric and retrocrural nodes. One patient failed to benefit and died shortly after completing 12 months of therapy. Bone marrow mastocytosis decreased by 5% to 10% after 12 months of therapy with IFN-alpha. Although five of the six patients had a decrease in the urinary excretion of 1-methyl-4-imidazole acetic acid, serum tryptase values did not appreciably change in any patient. Side-effects from IFN-alpha included hypothyroidism, thrombocytopenia and depression. It is concluded that although treatment with IFN-alpha was associated with a decline in bone marrow mastocytosis and reduced excretion of histamine metabolites, prolonged therapy may be needed and dose-limiting side-effects are frequent.
Assuntos
Interferon-alfa/uso terapêutico , Mastocitose/terapia , Idoso , Feminino , Seguimentos , Humanos , Imidazóis/urina , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Mastocitose/urina , Pessoa de Meia-Idade , Prurido/terapia , Proteínas Recombinantes , Urticaria Pigmentosa/terapiaRESUMO
The symptoms and hemodynamic alterations that accompany episodes of systemic mast cell activation have been largely attributed to excessive prostaglandin (PG)D2 release. Quantification of the major urinary metabolite of PGD2 has been invaluable in elucidating a role for PGD2 in these clinical entities and in the biochemical evaluation of systemic mastocytosis. With the use of a modified mass spectrometric assay for the major urinary metabolite of PGD2, this metabolite was detected in plasma from 10 normal volunteers (3.5 +/- 1.4 pg/ml). Ingestion of niacin, which induces endogenous release of PGD2, increased plasma levels of this metabolite 6.3 to 33 times above the upper limit of normal by 2 hours. Thereafter, levels declined gradually but remained elevated for up to 6 to 8 hours. In contrast, circulating levels of 9 alpha, 11 beta-PGF2, the initial metabolite of PGD2, peaked by 30 minutes and returned to baseline by 2 hours. The clinical utility of measuring the major urinary metabolite in the circulation was demonstrated by detection of markedly increased levels in plasma and serum from patients with systemic mastocytosis and a patient with a severe type I allergic reaction. Thus in the biochemical evaluation of episodes of systemic mast cell activation and endeavors to further elucidate the role of PGD2 in human disease, there are kinetic advantages of measuring the major urinary metabolite of PGD2 in the circulation. One particular advantage is the evaluation of clinical events, which only in retrospect are suspected to be associated with excessive release of PGD2, yet plasma or serum was obtained proximate to the event.