Urinary Catecholamine Metabolites Research Articles

Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection.

Pheochromocytomas and paragangliomas are often surgically curable. However, resection of these tumors can be life threatening. We undertook this study to determine the frequency of, and risk factors for, perioperative complications in patients undergoing resection of pheochromocytoma or paraganglioma. We retrospectively reviewed the medical records of patients during 1983-1996 who underwent surgical resection of catecholamine-secreting pheochromocytoma or paraganglioma. Preoperative risk factors, adverse intraoperative events, and complications occurring in the 30 days after operation were recorded. Blood pressures were collected from manual records. The ranked sum test and Fisher's exact test were used for analyses. Adverse perioperative events or complications occurred in 45 of 143 patients (31.5%; exact 95% confidence interval, 24.0% to 39.8%). Of these 45 patients, 41 experienced one or more adverse intraoperative events. The most common adverse event was sustained hypertension (36 patients). There were no perioperative deaths, myocardial infarctions, or cerebrovascular events. Preoperative factors univariately associated with adverse perioperative events included larger tumor size (P: = 0.007), prolonged duration of anesthesia (P: = 0.015), and increased levels of preoperative urinary catecholamines and catecholamine metabolites: vanillylmandelic acid (P: = 0.019), metanephrines (P: = 0.004), norepinephrine (P: = 0. 014), and epinephrine (P: = 0.004). Despite premedication of most patients with phenoxybenzamine and a beta-adrenergic blocker, varying degrees of intraoperative hemodynamic lability occurred. Few patients who had pheochromocytoma or paraganglioma resection experienced significant perioperative morbidity and none died in the largest retrospective study on this topic to date. This study confirms the very good perioperative outcomes demonstrated in smaller studies on this high-risk population, and identifies several risk factors for adverse outcomes.

Cardiac troponin I predicts myocardial dysfunction in aneurysmal subarachnoid hemorrhage

OBJECTIVESWe studied the incidence of myocardial injury in aneurysmal subarachnoid hemorrhage (SAH) using the more sensitive cardiac troponin I (cTnI) assay, correlated changes in cTnI with creatine kinase, MB fraction (CK-MB), myoglobin, and catecholamine metabolite assays, and examined the predictive value of changes in cTnI for myocardial dysfunction.BACKGROUNDMyocardial injury in aneurysmal SAH as evidenced by elevated CK-MB fraction has been reported. Little published data exist on the value of cTnI measurements in aneurysmal SAH.METHODSThirty-nine patients were studied for seven days. Clinical cardiovascular assessment, electrocardiographic (ECG), echocardiography, cTnI, CK, CK-MB and CK-MB index, myoglobin and 24-h urinary catecholamine assays were performed in all patients. The ECG abnormalities were defined by the presence of ST-T changes, prolonged QT intervals, and arrhythmias. An abnormal echocardiogram was defined by the presence of wall-motion abnormalities and a reduced ejection fraction. The severity of SAH was graded clinically and radiologically.RESULTSEight patients demonstrated elevations in cTnI (upper limit of normal is 0.1 μg/liter with the immunoenzymatic assay and 0.4 μg/liter with the sandwich immunoassay), while five had abnormal CK-MB levels (upper limit of normal is 8 μg/liter). Patients with more severe grades of SAH were more likely to develop a cTnI leak (p < 0.05). Patients with cTnI elevations were more likely to demonstrate ECG abnormalities (p < 0.01) and manifest clinical myocardial dysfunction (p < 0.01) as evidenced by the presence of a gallop rhythm on auscultation and clinical or radiological evidence of pulmonary edema as compared to those with CK-MB elevations. The sensitivity and specificity of cTnI to predict myocardial dysfunction were 100% and 91%, respectively, whereas the corresponding figures for CK-MB were 60% and 94%, respectively. Elevations in myoglobin levels (upper limit of normal <70 μg/liter) and urinary catecholamine metabolites (urinary vanilmandelate/creatinine ratio upper limit of normal, 2.6) are a nonspecific finding.CONCLUSIONSMeasurements of cTnI reveal a higher incidence of myocardial injury than predicted by CK-MB in aneurysmal SAH, and elevations of cTnI are associated with a higher incidence of myocardial dysfunction. Thus, cTnI is a highly sensitive and specific indicator of myocardial dysfunction in aneurysmal SAH.

Clinical prognostic factors in 1277 patients with neuroblastoma: results of The European Neuroblastoma Study Group ‘Survey’ 1982–1992

In 1982 the European Neuroblastoma Study Group (ENSG) established a prospective registry for patients with newly diagnosed neuroblastoma (‘The ENSG Survey’). Clinical information was collected primarily to: (a) establish an ENSG database; and (b) investigate prognostic factors in neuroblastoma. This paper summarises the results of the survey. By 1992, 1277 patients with a median age of 26 months (range: 0–289 months), gender ratio of 1.19 M:F had been registered from 30 centres. The median follow-up of survivors is 9.7 years (range: 1–14 years). Overall 5-year survival (S) is 45% (95% CI 42–48%), and event-free survival (EFS) is 43% (95% CI 40–45%). For both survival and EFS the key established prognostic factors, stage and age, are highly significant ( P<0.001). In particular, patients under 1 year of age at diagnosis, whatever the disease stage, had a more favourable prognosis than older patients; stage 2 (EFS 93% (95% (CI 85–97) versus 76% (95% CI 67–86), P=0.02), stage 3 (EFS 91% (95% CI 82–96) versus 52% (95% CI 44–60), P<0.001) and stage 4 (EFS 59% (95% CI 48–69) versus 16% (95% CI 13–19), P<0.001). Multivariate analysis established that the anatomical location of the primary tumour (i.e. abdominal versus other sites) and primary tumour volume also conferred a statistically significant difference. In stage 4 disease the 20% of patients without demonstrable bone marrow involvement had a more favourable prognosis than those with infiltrated marrow (EFS 36% (95% CI 13–19) versus 16% (95% CI 29–45), P<0.001). Urine catecholamine metabolite levels (raised versus normal), histology (ganglioneuroblastoma versus neuroblastoma) and gender had no significant effect on outcome after stage and age were accounted for. 5-year survival following first relapse is only 5.6% (95% CI 2.8–8.4). This ENSG Survey provides secure data for future comparisons with new prognostic factors and treatment programmes.

The Hemodynamic and Adrenergic Effects of Perioperative Dexmedetomidine Infusion after Vascular Surgery

We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia. The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients.

MANAGEMENT APPROACHES TO ADRENAL INCIDENTALOMAS (ADRENALOMAS): A View from Athens, Greece

We believe the management of adrenalomas should include the following: 1. A detailed history and physical examination to detect subtle evidence of hormonal hypersecretion or the possibility of metastatic carcinoma 2. Hormonal studies, such as The short dexamethasone suppression test (2 mg of dexamethasone) followed by a high-dose dexamethasone suppression test (8 mg), CRH assay, and analysis of the diurnal cortisol rhythm if serum cortisol is greater than 3 micrograms/dL 24-Hour (or spot) urinary catecholamine metabolites (metanephrine and normetanephrine) Plasma aldosterone level and renin activity in the hypertensive or normotensive patient with serum potassium less than 3.9 nmol/L 3. Additional imaging studies, such as MR imaging 131I-iodocholesterol (NP59) scanning to detect a subclinically functioning adenoma or carcinoma (MIBG scanning is rarely indicated) The role of FNA is limited. This modality may be helpful only in the patient with coexistent extradrenal carcinoma to confirm adrenal metastasis. Although genetic and molecular biology studies do not have wide clinical application, they should be encouraged and supported. Once all of these data are collected, the clinician should perform the following two steps: 1. All clearly nonfunctioning adrenalomas that are not suspicious for malignancy should be observed for several years, mainly with hormonal studies, until their secretory and benign nature is confirmed. 2. All patients with adrenalomas with evidence of subclinical function or potential for malignancy (using size, imaging, FNA, and molecular biology criteria) should undergo laparoscopic adrenalectomy for definitive diagnosis and therapy. The age, the overall medical condition, and the anxiety of the patient should be considered in the decision to operate on a patient with an adrenaloma.

Population-based and controlled study to evaluate neuroblastoma screening at one year of age in Germany: interim results.

The German Neuroblastoma Screening Project is the first controlled and population-based screening study to evaluate the presumed benefit of neuroblastoma mass screening at 1 year of age (10-18 months). Screening takes place in 6 of the 16 German states; children from the remainder serve as controls. The German Childhood Cancer Registry enables a mostly complete follow-up and detection of false-negative patients. Up to December, 1999, 1,199,165 children were examined for urinary catecholamine metabolites and 124 cases of neuroblastoma were detected preclinically, giving a detection rate of 10.3/100,000. Within this cohort, 33 false-negative cases were found. The results of this screening program will be crucial for further implementation of neuroblastoma screening.

Disomy 1 with terminal 1p deletion is frequent in mass-screening-negative/late-presenting neuroblastomas in young children, but not in mass-screening-positive neuroblastomas in infants.

The mass screening (MS) of neuroblastoma has been undertaken in Japan by measuring urinary catecholamine metabolites in infants at the age of 6 months. To clarify the biological characteristics of MS-positive (MS+) tumors in infants and MS-negative (MS-)/late-presenting tumors in young children, metaphase cytogenetic and/or interphase 2-color FISH analyses using terminal 1p and pericentromeric 1q probes were performed on 246 (186 MS+ and 60 MS-) patients with neuroblastomas. The 246 tumors were classified into 4 groups on the basis of the constitution of chromosome 1; 22 tumors had disomy 1 with no 1p deletion (Dis1Norm1p); 41 tumors had disomy 1 or tetrasomy 1, all with the 1p deletion (Dis1Del1p); 164 tumors had trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1, none with 1p deletion (Tris1Norm1p); 19 tumors with the same copy numbers of chromosome 1 as the Tris1Norm1p group, had 1p deletion (Tris1Del1p). mycn amplification was absent in the Dis1Norm1p and Tris1Del1p groups, frequent in the Dis1Del1p group (24/41), and rare in the Tris1Norm1p group (3/164) (p < 0.0001). Event-free survival at 5 years was lowest [19.5%; 95% confidence interval (CI), 5.1-33.9] in the Dis1Del1p group, highest in the Tris1Norm1p (96.3%; 95% CI, 93.5-99.2) and Tris1Del1p (94.7%; 95% CI, 84.7-104.8) groups, and intermediate but varied (54.5%; 95% CI, 33.7-75.4) in the Dis1Norm1p group (p < 0.0001). Of the MS+ tumors, 90% were Tris1Norm1p or Tris1Del1p, and 55% of the MS- tumors were Dis1Del1p. The finding that the Dis1Del1p tumors were frequent in MS- but not in MS+ tumors suggests the limited efficacy of the MS program into reducing mortality from neuroblastoma.

Dysphagia and regurgitation in a 10-year-old child.

A 10-year-old girl presented with a four-month history of progressive difficulties with swallowing, regurgitation and weight loss. Medical history did not reveal any episode of choking, dysphagia or respiratory symptoms....

The clinical use of fine needle aspiration cytology for diagnosis and management of children with neuroblastic tumours.

This study presents the results of fine needle aspiration cytology in a series of 26 consecutive children with neuroblastic tumours. The cytological spectrum varied from undifferentiated small tumour cells to mature ganglion cells in a fibrillar background. In 24 children with neuroblastic tumours at onset the cytological diagnosis was correct in 21 cases, whereas two aspirates yielded nondiagnostic necrotic material and a fibrillar material without tumour cells, respectively. One necrotic lymph node aspirate was initially incorrectly diagnosed as lymphoma, but the diagnosis was later revised to neuroblastoma. Suspected signs of disease progression or relapses were confirmed (n = 9) or ruled out (n = 1) using aspiration cytology. The diagnostic accuracy in the complete series was 97% (31/32) in cases with adequate smears. Immunocytochemistry confirmed the cytological diagnosis in 14 of 15 cases and was decisive in one. Elevated catecholamine metabolites in urine was detected in all children with a cytological diagnosis of neuroblastoma. General anaesthesia was only performed when coincidental invasive investigations (n = 13) were to be carried out or if the aspiration was intrathoracic (n = 6). It is concluded that aspiration cytology in conjunction with immunocytochemistry offers a safe, rapid and accurate diagnostic method which may be useful, together with analyses of catecholamine metabolites in urine, in the clinical management of children with neuroblastic tumours.

製造業従業員の循環器・自律神経機能 : (I)労働時間、疲労自覚症状、尿中カテコールアミン代謝物

製造業従業員の循環器・自律神経機能 : (I)労働時間、疲労自覚症状、尿中カテコールアミン代謝物

Screening for neuroblastoma is ineffective in reducing the incidence of unfavourable advanced stage disease in older children.

Neuroblastoma exhibits many characteristics which would suggest that preclinical detection may improve outcome. The Quebec Neuroblastoma Screening Project was initiated to determine whether mass screening could reduce mortality in a large cohort of infants. All 476,603 children born in the province of Quebec during a 5-year period of time (1 May 1989 to 30 April 1994) were eligible for determinations of urinary catecholamine metabolites at 3 weeks and 6 months of age. Children with positive screening were referred to one of four paediatric cancer centres in Quebec for uniform evaluation and treatment. Standardised incidence ratios (SIRs) were calculated for neuroblastoma in Quebec and two comparable population-based controls during the same period of time using similar ascertainment procedures. Compliance with screening in Quebec was 91% at 3 weeks (n = 425,816) and 74% at 6 months (n = 349,706). Up to 31 July 1995 with a follow-up of the birth cohort of 15-75 months, 118 cases of neuroblastoma were diagnosed, 43 detected preclinically by screening, 20 detected clinically prior to screening at 3 weeks of age and 55 detected clinically after 3 weeks of age having normal screens (n = 52) or never screened (n = 3). Based on data from concurrent control populations, 54.5 cases of neuroblastoma would have been expected in Quebec during the study period for an SIR of 2.17 (95% CI 1.79-2.57, P < 0.0001). For the two control groups, the overall SIR was 1.00 (NS). SIRs for Quebec by age at diagnosis in yearly intervals show a marked increased incidence under 1 year of age (SIR = 2.85, 95% CI 2.26-3.50), with no reduction in incidence in subsequent years. We conclude that screening for neuroblastoma markedly increases the incidence in infants without decreasing the incidence of unfavourable advanced stage disease in older children. It is unlikely that screening for neuroblastoma in infants will reduce the mortality of this disease.

A neuroblastoma cell line derived from a case detected through a mass screening system in Japan

BACKGROUND A mass screening system in Japan, which involves measuring urinary catecholamine metabolites, has resulted in an increasing number of cases of neuroblastoma, most of which have favorable biologic properties and some of which are associated with tumor regression or involution. At the time this study was begun, the characteristics and biologic nature of the neuroblastomas had not been fully defined, because a cell line had not yet been established with tumor tissue taken from a neuroblastoma detected in the mass screening. METHODS The authors established a cell line by tissue culture for over 50 generations from a neuroblastoma found during mass screening, which was characterized by favorable histology, with a triploid DNA stemline and without N-myc gene amplification. The morphologic and biologic characteristics of the new cell line were investigated in vitro. RESULTS The cell line, designated MASS-NB-SCH-1, has neuronal properties, such as neurite-like processes and neurofilaments, as well as the expression of vimentin and fibronectin in studies of the cell morphology and immunohistochemistry. Karyotype analysis detected the presence of 42-46 chromosomes, with a deletion of the short arm of 1 of the 3 copies of chromosome 1. DNA ploidy was near-diploid in association with 20-fold amplification of N-myc genes. CONCLUSIONS The cell line has a nature distinct from the original tumor tissue. It may be characterized by phenotypic change caused by clonal selection or evolution of aggressive, proliferative properties in vitro. This cell line will be a useful model to investigate the properties of the neuroblastoma in relation to the N-myc amplification mechanism. Cancer 1997; 79:2036-44. © 1997 American Cancer Society.

A neuroblastoma cell line derived from a case detected through a mass screening system in Japan

BACKGROUND A mass screening system in Japan, which involves measuring urinary catecholamine metabolites, has resulted in an increasing number of cases of neuroblastoma, most of which have favorable biologic properties and some of which are associated with tumor regression or involution. At the time this study was begun, the characteristics and biologic nature of the neuroblastomas had not been fully defined, because a cell line had not yet been established with tumor tissue taken from a neuroblastoma detected in the mass screening. METHODS The authors established a cell line by tissue culture for over 50 generations from a neuroblastoma found during mass screening, which was characterized by favorable histology, with a triploid DNA stemline and without N-myc gene amplification. The morphologic and biologic characteristics of the new cell line were investigated in vitro. RESULTS The cell line, designated MASS-NB-SCH-1, has neuronal properties, such as neurite-like processes and neurofilaments, as well as the expression of vimentin and fibronectin in studies of the cell morphology and immunohistochemistry. Karyotype analysis detected the presence of 42-46 chromosomes, with a deletion of the short arm of 1 of the 3 copies of chromosome 1. DNA ploidy was near-diploid in association with 20-fold amplification of N-myc genes. CONCLUSIONS The cell line has a nature distinct from the original tumor tissue. It may be characterized by phenotypic change caused by clonal selection or evolution of aggressive, proliferative properties in vitro. This cell line will be a useful model to investigate the properties of the neuroblastoma in relation to the N-myc amplification mechanism. Cancer 1997; 79:2036-44. © 1997 American Cancer Society.

Paediatric reference values for urinary catecholamine metabolites evaluated by high performance liquid chromatography and electrochemical detection.

The majority of the published reference range data on catecholamines excretion by healthy children is incomplete and often contradictory (1). We assayed in the urines of 127 healthy children the values of the catecholamines (norepinephrine, epinephrine, dopamine) and their methylated metabolites (normetanephrine, metanephrine, 3-methoxytyramine) for the determination of paediatric reference ranges. Data were expressed as micrograms/24 h, mumol/24 h and mmol/mol creatinine. An isocratic HPLC procedure by ion-pair reversed phase chromatography on a C18 column, using a single mobile phase containing formic acid, acetonitrile, diethylamine and octane sulphonic acid (ion pairing agent), permitted the separate assay of the various fractions of total catecholamines. The relations between each biogenic amine and age were studied and reference values were determined as a function of age.

Urinary excretion of methylated catecholamine metabolites in a child with neuroblastoma maturing into ganglioneuroma

Neuroblastomas are malignant tumors derived embryonically from the neural crest. Biological diagnosis relies on assay of urinary excretion of homovanillic acid (HVA), vanillylmandelic acid (VMA), and dopamine (DA). Spontaneous regression of these neoplasms has been reported by numerous investigators. The authors report the case of a child with neuroblastoma that illustrates the relationship between catecholamine metabolites and tumor maturation. At 1 month of age, this infant presented an adrenal neuroblastoma with multiple metastases (stage IV); the initial histological diagnosis based on examination of cutaneous metastases was neuroblastoma. At the age of 6 months, after chemotherapy, the primary tumor was resected; hepatic metastases were discovered at laparotomy. The histological diagnosis for all lesions was highly differentiated, mature ganglioneuroma-like tissue. The main biochemical abnormality at the time of diagnosis was an elevation in normetanephrine (NMN). HVA was only slightly increased but rose progressively during chemotherapy; it dropped back to normal levels after the sixth course. This case illustrates the potential benefits of separate assays of urinary methylated catecholamine metabolites for biochemical diagnosis and therapeutic management of neuroblastoma in addition to assays of HVA, VMA, and DA. Case findings suggest existence of a transformation process with maturation of the tumor involving enzymatic regulation and expression of MAO. © 1996 Wiley-Liss, Inc.

Urinary excretion of methylated catecholamine metabolites in a child with neuroblastoma maturing into ganglioneuroma

Neuroblastomas are malignant tumors derived embryonically from the neural crest. Biological diagnosis relies on assay of urinary excretion of homovanillic acid (HVA), vanillylmandelic acid (VMA), and dopamine (DA). Spontaneous regression of these neoplasms has been reported by numerous investigators. The authors report the case of a child with neuroblastoma that illustrates the relationship between catecholamine metabolites and tumor maturation. At 1 month of age, this infant presented an adrenal neuroblastoma with multiple metastases (stage IV); the initial histological diagnosis based on examination of cutaneous metastases was neuroblastoma. At the age of 6 months, after chemotherapy, the primary tumor was resected; hepatic metastases were discovered at laparotomy. The histological diagnosis for all lesions was highly differentiated, mature ganglioneuroma-like tissue. The main biochemical abnormality at the time of diagnosis was an elevation in normetanephrine (NMN). HVA was only slightly increased but rose progressively during chemotherapy; it dropped back to normal levels after the sixth course. This case illustrates the potential benefits of separate assays of urinary methylated catecholamine metabolites for biochemical diagnosis and therapeutic management of neuroblastoma in addition to assays of HVA, VMA, and DA. Case findings suggest existence of a transformation process with maturation of the tumor involving enzymatic regulation and expression of MAO.

Indolent course of advanced neuroblastoma in children older than 6 years at diagnosis.

An early observation suggests that children older than 6 years of age at diagnosis of neuroblastoma constitute a favorable prognostic group. Kaplan-Meier plots of survival of all such patients diagnosed at the Children's Hospital of Pittsburgh 1975-1992 were compared with curves of concurrently treated patients with Stage IV disease who were 1-6 years of age at diagnosis ("younger patients"). Known prognostic features, including stage and primary site of disease, pattern of metastases, histopathology, MYCN gene amplification, and urinary catecholamine metabolite ratios, were reviewed. Of 17 children diagnosed after the age of 6 years ("older patients"), 13 patients had Evans' Stage IV disease and 4 had Stage III disease. The median survival was 3.24 years (range, 0.63-15.04 years) for the entire cohort and 3.07 years for those children with Stage IV disease. This compared with a median survival of 1.05 years in 34 concurrent younger patients (P < 0.01). In most cases, disease in these older patients was characterized by a short-lived complete or partial remission followed by aggressive recurrent disease that was partially and only transiently chemo- or radiosensitive. Only 3 patients (2 with Stage IV disease) are in continuous complete remission at 3, 5 10/12, and 14 1/2 years from diagnosis. Although poor prognostic factors were common, including the presence of bony metastases (12/17), biopsy material from pretreatment tumor specimens demonstrated a single MYCN gene copy number in all patients and favorable histology in 15 of 16 samples. Older children with neuroblastoma have a more indolent course than do younger patients, a finding that appears to be related to favorable histology and the absence of MYCN amplification. Examination of larger numbers of such patients from cooperative groups should lead to a better understanding of what appears to be a subset of pediatric patients with neuroblastoma who may benefit from specifically tailored treatment protocols.

Modification of a tunable UV-visible capillary electrophoresis detector for simultaneous absorbance and fluorescence detection: profiling of body fluids for drugs and endogenous compounds

Using fused-silica optical fibres for fluorescence light collection and bandpass filters for selection of emission wavelengths, a capillary electrophoresis detection cell of a conventional, tunable UV-Vis absorbance detector was adapted for simultaneous fluorescence (at selected emission wavelength) and absorbance (at selected excitation wavelength) detection. Detector performance is demonstrated with the monitoring of underivatized fluorescent compounds in body fluids by micellar electrokinetic capillary chromatography with direct sample injection. Compared with UV absorption detection, fluorescence detection is shown to provide increased selectivity and for selected compounds also up to tenfold higher sensitivity. Examples studied include screening for urinary indole derivatives (tryptophan, 5-hydroxytryptophan, tyrosine, 3-indoxyl sulfate and 5-hydroxyindole-3-acetic acid) and catecholamine metabolites (homovanillic acid and vanillylmandelic acid) and the monitoring of naproxen in serum, quinidine in serum and urine and of salicylate and its metabolites in serum and urine.

Pattern of elevation of urine catecholamines in intracerebral haemorrhage.

Autonomic nervous system dysfunction is a common complication of severe intracranial disease. The aim of this study was to reveal the autonomic changes in patients suffering from acute intracerebral haemorrhage (ICH). 25 patients with spontaneous ICH within 24 hours of onset of symptoms were included. All patients were treated with standardised medical management and the meta- and normetanephrines were detected by high performance liquid chromatography (HPLC) in 24-hour urine every day. The mean level of normetanephrine (709 +/- 579 micrograms/day) and metanephrine (244 +/- 161 mg/day) were significantly elevated in comparison with a control group, p < or = 0.01. The norepinephrine elevation was of greater diagnostic and prognostic importance. Maximum urinary catecholamine metabolite levels occurred between day 3 to 10 after the bleeding. Normetanephrines correlated with the prognosis and the complications of ICH: intraventricular involvement resulted in significantly elevated normetanephrine levels (896 +/- 520 micrograms/day versus 311 +/- 78 micrograms/day) p < or = 0.01. Patients with a great volume of haematoma developed severe autonomic dysregulation (normetanephrines 1114 +/- 493 micrograms/day), whereas patients with smaller haematoma did not (339 +/- 125 micrograms/day) p < or = 0.0001; patients with bad outcome (1014 +/- 620 mg/day) had higher levels of normetanephrines than those with a good prognosis (322 +/- 110 micrograms/day) p < or = 0.001. A close relationship to elevated intracranial pressure was established. This study demonstrated the feasibility of detecting autonomic nervous system dysfunction in neurological intensive care patients by means of examination of the metabolites of the catecholamines in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Buspirone on Urinary Catecholamine Assays

To the Editor: Many medications interfere with the assays for catecholamine metabolites in urine that are used to evaluate patients suspected of having a pheochromocytoma.1,2 We report the effect o...