Measurement Of Homovanillic Acid Research Articles

Establishment and clinical application of a candidate reference measurement procedure for quantification of urinary vanillylmandelic acid and homovanillic acid using ID-LC-MS/MS method

Neuroblastoma (NB), an embryonic tumor of the autonomous nervous system, poses a significant threat to the health and lives of children. Accurate measurement of vanillylmandelic acid (VMA) and homovanillic acid (HVA) in human urine is crucial for screening and diagnosis of NB. Although various laboratories have developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect VMA and HVA, the comparability between the results obtained from different laboratories and methods was poor. The absence of reference method for VMA and HVA hinders the standardization of their measurements. Therefore, a candidate reference measurement procedure (cRMP) based on isotope dilution LC-MS/MS (ID-LC-MS/MS) for the detection of VMA and HVA in human urine was established. Urine samples were spiked with VMA-d3 and HVA-d5 as internal standards and extracted using a protein precipitation method. The cRMP exhibited desirable precision with the total imprecision below 5 %. The accuracy of this cRMP was demonstrated by the high analytical recovery (98.64 % - 102.22 % and 98.41 % - 100.97 % for VMA and HVA, respectively), and comparability between different reference systems. The limit of detection for HVA and VMA were 15.625 ng/mL and 3.906 ng/mL, respectively; the quantification limits were 62.5 ng/mL and 7.813 ng/mL, respectively, which can meet the clinical detection requirements. The linear range was from 78.125 ng/mL to 20 μg/mL. Specificity evaluations showed no corresponding interference from structurally similar analogs. In conclusion, we have established a cRMP based on ID-LC-MS/MS for the measurement of VMA and HVA in urine samples, demonstrating well-defined method performance including accuracy, precision, and specificity. This newly established cRMP is suitable for routine assay standardization and evaluation of clinical samples. Furthermore, this method has the potential to significantly enhance the diagnostic accuracy for neuroblastoma.

A Simple, Fast, and Reliable LC-MS/MS Method for the Measurement of Homovanillic Acid and Vanillylmandelic Acid in Urine Specimens.

Homovanillic acid (HVA) and vanillylmandelic acid (VMA) are catecholamine metabolites used in the diagnostic workup of neuroendocrine tumors. Here we describe a simple dilute-and-shoot method for simultaneously quantitating HVA and VMA in human urine specimens. The method employs analyte separation on a reverse-phase liquid chromatography column followed by detection using electrospray ionization triple quadrupole mass spectrometry (ESI-MS/MS), wherein qualifier and quantifier ion transitions are monitored. This is a simple and fast analytical method with an injection-to-injection time of 4min.

Simple dilute-and-shoot method for urinary vanillylmandelic acid and homovanillic acid by liquid chromatography tandem mass spectrometry

BackgroundNeuroblastomas are pediatric tumors characterized by overproduction of catecholamines. The catecholamine metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA), are used in clinical evaluation of neuroblastoma. Tandem mass spectrometry (LC-MS/MS) is an effective analytical method for measurement of VMA and HVA in urine. MethodsDilute-and-shoot sample preparation was performed in a 96-well format using a liquid handler. Chromatographic separation was achieved using a reverse phase column; detection was accomplished by triple quadrupole mass spectrometry with electrospray ionization in positive mode. Data were acquired by multiple reaction monitoring. Two transitions, quantifier and qualifier, were monitored for each analyte and its stable isotope-labeled internal standard. Analytical specificity studies were performed. ResultsInjection-to-injection time was 4min. The method was validated for linearity, limit of quantification, imprecision, accuracy, and interference. Linearity was 0.5–100mg/l for both analytes. Within-run, between-day, and total imprecision were 1.0–4.1% for VMA and 0.8–3.8% for HVA. The method correlated well with our established HPLC method. Interferences precluding quantitation of VMA in 3% of specimens were reduced significantly (to 0.1% of specimens) using a modified LC gradient to reanalyze affected samples. ConclusionsA simple, robust, economical, fast LC-MS/MS method was developed and validated for measurement of urinary VMA and HVA.

Short prolactin profile for monitoring treatment in BH4 deficiency

Tetrahydrobiopterin (BH4) deficiency causes hyperphenylalaninemia and impaired synthesis of serotonin and dopamine, leading to brain degeneration and early death if left untreated. Replacement therapy with neurotransmitters precursors is the cornerstone of treatment, relying on 5-hydroxytryptophan and l-dopa administration. Effective restoration of dopaminergic activity is thickened, like in Parkinson's disease, by the pulsatile pharmacokinetic profile of l-dopa. Monitoring of l-dopa therapy in BH4 deficiency is generally based upon clinical observation and periodical measurement of homovanillic acid (HVA) concentration in the cerebrospinal fluid (CSF). According to the finding that dopamine is the natural inhibitor of prolactin (PRL) incretion, we introduced the use of peripheral PRL measurement as an index of dopaminergic homeostasis, so avoiding the need of repeated lumbar punctures in patients with BH4 deficiency. As a single PRL evaluation can be misleading, due to the dependency of PRL fluctuations on l-dopa administration schedule, here we show that a short PRL profile is suitable for monitoring these patients. Together with the assessment of patients' clinical symptoms, this standardized tool will ensure an objective non-invasive reference to the management of dopaminergic replacement therapy in BH4 deficiency, even in patients treated with dopamine agonists.

V4-13 LEFT-SIDED LAPAROSCOPIC PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA

You have accessJournal of UrologyAdrenal/Robotics1 Apr 2014V4-13 LEFT-SIDED LAPAROSCOPIC PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA Omer Demir, Ozan Bozkurt, Tevfik Demir, Canan Altay, Mustafa Secil, and Adil Esen Omer DemirOmer Demir More articles by this author , Ozan BozkurtOzan Bozkurt More articles by this author , Tevfik DemirTevfik Demir More articles by this author , Canan AltayCanan Altay More articles by this author , Mustafa SecilMustafa Secil More articles by this author , and Adil EsenAdil Esen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1546AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Laparoscopic partial adrenalectomy or adrenal sparing surgery originated from the aim of preserving functioning gland in order to obviate the need for hormonal replacement and undesired side effects. A case of left-sided laparoscopic partial adrenalectomy for phechromocytoma and technical aspects are presented in this video. Methods A 54 year old female patient was referred to our hospital with a 4 cm left adrenal mass in ultrasonographic examination. She has been on medication for HT for 2 years and she was complaining of flushing and palpitation. Endocrinologic work-up consisted of plasma thyroid hormone levels, plasma catecholamine and basal cortisol levels, ACTH supression test, 24-hour urinary measurement of cortizol and catecholamines. She underwent PET-CT imaging for radiologic diagnosis. She was prescribed alpha-blocker therapy 1-month before surgery and left-sided laparoscopic partial adrenalectomy with lateral transperitoneal approach using 3 entry ports was performed. Intraoperative laparoscopic color doppler ultrasonography confirmed the viability and vascular supply of the remaining adrenal gland. Results Thyroid hormone levels and plasma catecholamine and basal cortisol levels were in normal ranges and ACTH suppression test was negative. 24-hour urinary measurement of homovanillic acid (HVA) level was slightly higher than normal levels with 10.73 mg/24h (Reference ranges: 0.5-6.2 mg/24h) whereas vanillylmandelic acide (VMA), metanephrine and normetanephrine levels were in normal ranges. PET-CT imaging supported the diagnosis of pheochromocytoma. Operation was performed under general anesthesia and the operation time was 45 minutes. No peroperative or postoperative complication was encountered and the patient was discharged one day after the surgery. Pathologic examination revealed pheochromocytoma. Conclusions Laparoscopic partial adrenalectomy might be attempted for excision of pheochromocytoma whenever feasible. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e554 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Omer Demir More articles by this author Ozan Bozkurt More articles by this author Tevfik Demir More articles by this author Canan Altay More articles by this author Mustafa Secil More articles by this author Adil Esen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Serotonin Metabolites in the Cerebrospinal Fluid in Sudden Infant Death Syndrome

Forensic biomarkers are needed in sudden infant death syndrome (SIDS) to help identify this group among other sudden unexpected deaths in infancy. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. As a first step toward their assessment as forensic biomarkers of medullary pathology, here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared with those of autopsy controls. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high-performance liquid chromatography in 52 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude the use of 5-HIAA, HVA, Trp, or Tyr measurements as CSF autopsy biomarkers of 5-HT medullary pathology in infants who have died suddenly and unexpectedly. They do, however, provide important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS.

Influence of saliva flow rate stimulated by gum-chewing on salivary concentrations of catecholamine metabolites

BackgroundThe measurement of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) in saliva is useful for diagnosis of some psychiatric disorders. Gum-chewing increases salivation and is sometimes used to collect an adequate sample volume of saliva within a shorter time. However, the rate of saliva production may affect the salivary concentrations of these catecholamine metabolites. We clarified whether the salivary concentrations of HVA and MHPG are dependent on the rate of salivation. MethodsStimulated saliva was collected from healthy volunteers chewing a tasteless and flavorless chewing gum after unstimulated saliva was collected without gum-chewing. The salivary HVA and MHPG concentrations were measured using newly developed LC/ESI-MS/MS methods. ResultsThe salivary HVA and MHPG concentrations were reproducibly measured when saliva was collected without gum-chewing (unstimulated saliva). In contrast, their salivary concentrations significantly decreased when salivation was stimulated by gum-chewing (p<0.05, Wilcoxon signed-rank test). ConclusionsStimulated saliva by gum-chewing should be used with caution in the measurement of the catecholamine metabolites. LogD is a useful indicator, when predicting whether the salivary concentration of a compound is dependent on the rate of salivation.

A Prospective Study of Expectant Observation as Primary Therapy for Neuroblastoma in Young Infants

To demonstrate that expectant observation of young infants with small adrenal masses would result in excellent event-free and overall survival. Neuroblastoma is the most common malignant tumor in infants, and in young infants, 90% of neuroblastomas are located in the adrenal gland. Although surgical resection is standard therapy, multiple observations suggest that expectant observation could be a safe alternative for infants younger than 6 months who have small adrenal masses. A prospective study of infants younger than 6 months with small adrenal masses and no evidence of spreading beyond the primary tumor was performed at participating Children's Oncology Group institutions. Parents could choose observation or immediate surgical resection. Serial abdominal sonograms and urinary vanillylmandelic acid and homovanillic acid measurements were performed during a 90-week interval. Infants experiencing a 50% increase in the volume of the mass, urine catecholamine values, or an increase in the homovanillic acid to vanillylmandelic acid ratio greater than 2, were referred for surgical resection. Eighty-seven eligible patients were enrolled: 83 elected observation and 4 chose immediate surgery. Sixteen observational patients ultimately had surgery; 8 had International Neuroblastoma Staging System stage 1 neuroblastoma, 2 had higher staged neuroblastoma (2B and 4S), 2 had low-grade adrenocortical neoplasm, 2 had adrenal hemorrhage, and 2 had extralobar pulmonary sequestration. The 2 patients with adrenocortical tumors were resected because of a more than 50% increase in tumor volume. The 3-year event-free survival for a neuroblastoma event was 97.7 ± 2.2% within the entire cohort of patients (n = 87). The 3-year overall survival was 100%, with a median follow-up of 3.2 years. Eighty-one percent of patients on the observation arm were spared resection. Expectant observation of infants younger than 6 months with small adrenal masses led to excellent event-free survival and overall survival while avoiding surgical intervention in a large majority of the patients.

Simultaneous determination of vanillylmandelic acid, homovanillic acid and creatinine in random urine by high performance capillary electrophoresis

Objective To establish a method for detecting urinary vanillylmandelic acid (VMA), homovanillic acid (HVA) and creatinine (Cr) simultaneously by high performance capillary electrophoresis (HPCE). Methods The separations were carried out using a 120 mmol/L phosphate buffer (pH 6.80) in a fused-silica capillary tube of 47 cm×75 μm I.D. by capillary zone electrophoresis (CZE). Injections were made by using the pressure mode for 4 s at 1 p. s. i. after samples were centrifuged and diluted. The detections were monitored by a diode-array detector (DAD) at 200 nm after samples were separated at a voltage of 20 kV. The method developed was validated systematically and applied to urine samples from healthy adults (n = 100) and children (n = 100) for establishing the reference ranges of VMA/Cr and HVA/Cr, respectively. Results Under these conditions, the separations of VMA, HVA and Cr could be completed within 13 min. The linearity ranges of VMA, HVA and Cr were 0-500, 0-500 and 0-4 000 μmol/L, respectively, with the correlation coefficients (r) between 0.997 2 and 0. 999 1 (P < 0.01). The detection limits (S/N= 3) were 1.0 μmol/L for VMA, 1.0 μmol/L for HVA and 50.0 μmol/L for Cr. The mean within-run (n = 10) CVs of migration time for VMA, HVA and Cr in urine were 0.58%, 0.56% and 0.25% respectively, while the mean between-run (n = 10) CVs of migration time were 0.95%, 1.00% and 0.48% respectively. The mean within-run (n = 10) CVs of peak area for VMA, HVA and Cr were 3.78%, 3.97% and 2.76% respectively, while the mean between-rim (n = 10) CVs of peak area were 4.60%, 4.08% and 4.42% respectively. The average recoveries were 98.36% for VMA, 93.56% for HVA and 98.85% for Cr. Other compounds in human urine such as catecholamines, 5-hydroxytryptamine and albumen didn't interfere with the assay. The correlation between CE method and HPLC method was good. And the correlation coefficients (r) of VMA and HVA were 0.954 9(P <0.01) and 0.945 1 (P < 0.01), respectively. Skewness distributions were presented for VMA/Cr and HVA/Cr in random urine from both adults and children, and the 95% reference ranges were established by the percentile method. For adults, the reference ranges of VMA/Cr and HVA/Cr were 0-4. 26 and 0-1.69 (μmol/mmol), respectively. For children, the reference ranges of VMA/Cr and HVA/Cr were 0-10.39 and 0-4.31 (μmol/mmol), respectively. Conclusions The CE method devised here for direct measurement of urinary VMA, HVA and Cr is simple, fast,precise and automatic with good repeatability. It is an ideal method for routine detection and mass screening of pheochromocytoma and neuroblastoms. Key words: Electropberesis; capillary; Vanilmandelic acid; Homovanillic acid; Creatinine; Urine.

Simultaneous detection of ascorbic acid, uric acid and homovanillic acid at copper modified electrode

The copper was deposited on glassy carbon (GC) and indium tin oxide (ITO) electrodes by electrochemical method. The copper structures on electrode were characterized by atomic force microscope, X-ray diffractometeric pattern and differential pulse voltammetric studies. Optimal conditions for uniform growth of copper structures on the electrode were established. Voltammetric sensor was fabricated using the copper deposited GC electrode for the simultaneous detection and determination of uric acid (UA) and homovanillic acid (HVA) in the presence of excess concentrations of ascorbic acid (AA). The voltammetric signals due to AA and UA oxidation were well separated with a potential difference of 400 mV and AA did not interfere with the measurement of UA and HVA at the GC/Cu electrode. Linear calibration curves were obtained in the concentration range 1–40 μM for AA and 20–50 μM for UA at physiological pH and a detection limit of 10 nM of UA in the presence of 10-fold excess concentrations of AA was achieved. The simultaneous detection of submicromolar concentrations of AA, UA and HVA was achieved at the GC/Cu electrode. The practical utility of the present GC/Cu modified electrode was demonstrated by measuring the AA content in Vitamin C tablet, UA content in human urine and blood serum samples with satisfactory results.

Reproducibility of plasma catecholamine metabolites in normal subjects

Plasma homovanillic acid (HVA) and methoxy-hydroxy-phenylglycol (MHPG) are often used in repeated measurement designs to assess dopamine and norepinephrine metabolism in clinical research. However, only limited data on the reproducibility of these metabolites are currently available. Plasma HVA and MHPG were measured in normal volunteers on five nonconsecutive mornings under fasting conditions and restricted smoking and physical activity. Intraclass correlation coefficients (ICC) for plasma HVA and MHPG across 5 days were determined to be 0.85 and 0.79, respectively. ICC improved to 0.90 for HVA and 0.91 for MHPG when the average of the first 2 days was examined against the average of the last 2 days. Results suggested that under controlled conditions plasma HVA and MHPG measurements have good reproducibility.

A study of the potential confounding effects of diet, caffeine, nicotine and lorazepam on the stability of plasma and urinary homovanillic acid levels in patients with schizophrenia

Ten men inpatients who met DSM-III-R criteria for schizophrenia participated. On five occasions at least one week apart, each subject had an intravenous line placed at 0730 after an overnight fast. On each occasion blood samples were drawn at 0800 and hourly thereafter through 1200 noon for measurement of plasma homovanillic acid (HVA). Total four-hour urine collections were obtained for measurement of urinary HVA. Subjects received five experimental conditions, in randomized sequence: no intervention, smoking one cigarette per hour, drinking one caffeinated cola per hour, lorazepam 2 mg IV push, or a high monoamine meal. Baseline (0800) plasma HVA measures showed only minor intrinsic variability. The average standard deviation in baseline plasma HVA over five occasions of measurement was low relative to the changes in HVA produced during treatment with antipsychotic medications. The high monoamine meal significantly elevated plasma HVA, with a similar trend for urinary HVA. Neither caffeine, nicotine, nor lorazepam significantly affected plasma or urinary HVA.

Influence of renal clearance on peripheral homovanillic acid measurements in healthy subjects and schizophrenic patients

In order to investigate the effect of renal clearance on plasma homovanillic acid (HVA) concentrations, we examined plasma concentration and urinary excretion of HVA and creatinine per 4 h over 24 h in eight male schizophrenic patients and eight healthy male subjects. Renal clearances of HVA and of creatinine were determined per 4 h period. No significant differences were found between groups in the total 24 h excretion of either HVA or creatinine. Although differences between groups in plasma HVA concentrations and urinary HVA excretion per 4 h did not reach statistical significance, the renal clearance of HVA was significantly lower in the patient group than in the control group. There was no difference between groups in creatinine clearance. Diurnal changes were seen in the renal clearance of HVA and creatinine in both groups. Renal HVA clearance decreased from 23.00–07.00 h, with a coincident decrease in urinary HVA excretion and an increase in plasma HVA concentration. We provide evidence that renal clearance is an important determinant of plasma HVA concentration, and should be considered when interpreting plasma HVA data.

Rapid and reliable high-performance liquid chromatographic method for analysing human plasma serotonin, 5-hydroxyindoleacetic acid, homovanillic acid and 3,4-dihydroxyphenylacetic acid

The simultaneous measurement of homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in human plasma by an ultrafiltration and microbore high-performance liquid chromatography—electrochemical detection technique is established. Conventional preparation of blood is very tedious and time-consuming, but isocratic separation of the analytes in plasma ultrafiltrates using a microbore column could be achieved within 10 min. Hence, theoretically, over 140 analyses can be performed in a working day. The detection limit (signal-to-noise ratio = 3) of this method is about 0.1–0.5 pg per injection for all analytes. The required volume of plasma samples can be less than 100 μl. Hence, blood loss is minimal, especially in repeated blood sampling. This rapid, simple and sensitive method can, therefore, be used as a routine clinical tool in the simultaneous measurement of plasma homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid.

Past and Future of Neuroblastoma Screening in Japan

In Japan, neuroblastoma is a common malignant tumor for children and its prognosis is unfavorable. Since this tumor excretes excessive amounts of vanillylmandelic acid (VMA) and homovanillic acid (HVA), catecholamine metabolites, into urine, both are sensitive diagnostic markers for neuroblastoma. In 1974, to improve the prognosis for neuroblastoma, a mass screening program by a qualitative VMA spot test for early detection of this tumor for 6-month-old infants was started in Kyoto, Japan. Subsequently, mass screening was also conducted in other areas in Japan. In 1985, mass screening commenced as a nationwide program throughout Japan, and in 1988, screening by quantitative measurement of VMA, HVA, and creatinine was recommended by the Ministry of Health and Welfare. During the 6 years from 1984 to 1989, 468 cases of neuroblastoma were detected from among 5,052,165 infants screened by this program. Analysis of findings in the 357 cases detected by mass screening from its inception in Kyoto until December of 1988 have been presented. The survival rate for these cases was 97% (348 of 357 cases). The prognosis of tumors detected by mass screening has clearly been favorable. In addition, survival rates were improved for all cases of neuroblastoma in Kyoto after the introduction of mass screening. The increased incidence of neuroblastoma in infants and the change in age distribution of all cases of neuroblastoma following the inception of urinary screening as well as the occurrence of spontaneous regression of neuroblastoma in relation to the screening program are discussed. Future problems facing mass screening for neuroblastoma are also presented.

Past and Future of Neuroblastoma Screening in Japan

In Japan, neuroblastoma is a common malignant tumor for children and its prognosis is unfavorable. Since this tumor excretes excessive amounts of vanillylmandelic acid (VMA) and homovanillic acid (HVA), catecholamine metabolites, into urine, both are sensitive diagnostic markers for neuroblastoma. In 1974, to improve the prognosis for neuroblastoma, a mass screening program by a qualitative VMA spot test for early detection of this tumor for 6-month-old infants was started in Kyoto, Japan. Subsequently, mass screening was also conducted in other areas in Japan. In 1985, mass screening commenced as a nationwide program throughout Japan, and in 1988, screening by quantitative measurement of VMA, HVA, and creatinine was recommended by the Ministry of Health and Welfare. During the 6 years from 1984 to 1989, 468 cases of neuroblastoma were detected from among 5,052,165 infants screened by this program. Analysis of findings in the 357 cases detected by mass screening from its inception in Kyoto until December of 1988 have been presented. The survival rate for these cases was 97% (348 of 357 cases). The prognosis of tumors detected by mass screening has clearly been favorable. In addition, survival rates were improved for all cases of neuroblastoma in Kyoto after the introduction of mass screening. The increased incidence of neuroblastoma in infants and the change in age distribution of all cases of neuroblastoma following the inception of urinary screening as well as the occurrence of spontaneous regression of neuroblastoma in relation to the screening program are discussed. Future problems facing mass screening for neuroblastoma are also presented.

Serial measurement of urinary VMA and HVA levels from one infant: A study for neuroblastoma mass screening

Urinary vanillylmandelic acid (VMA), homovanillic acid (HVA), and creatinine in 188 samples from one infant during the ages of 1 to 12 months were measured serially by high-performance liquid chromatography (HPLC). The mean VMA and HVA levels of the total 188 samples in this study were 11.9 ± 1.39 and 22.9 ± 2.92 μg/mg creatinine with coefficients of variation (CVs) 11.7% and 12.8%, respectively; and of 76 samples from 5 to 12 months of age, 12.3 ± 0.84 and 23.1 ± 2.03 μg/mg creatinine with CVs 6.8% and 8.8%. The CVs of VNA and HVA levels expressed in microgram per milligram of creatinine had decreased after 6 months of age (VMA, 5.0% to 8.3%, HVA, 5.3% to 8.4%). Chromatograms demonstrated the similar pattern from 1 to 12 months of age, although the infant had been fed foods typical in Japan, which included breast milk, seasonal fruits, vegetables, fish, chicken, and meat. Diurnal fluctuations of VMA and HVA levels in urine were not significant. When HPLC is used for measurement of VMA, HVA, and creatinine, it is not necessary to restrict foods that cause false-positive results in the qualitative VMA test from the infant's diet. Furthermore, random urine samples obtained throughout the 12 months could be effectively used for the measurement of these substances.

Homovanillic Acid Measurement in Clinical Research: A Review of Methodology

Despite its serious limitations, measuring the concentrations of homovanillic acid (HVA) in body fluids is perhaps the most direct method currently available to assess the changing activity of central dopamine (DA) neurons in living humans. The concentrations of HVA in body fluids are determined not only by the activity of central DA neurons but also by a number of unrelated factors such as the other sources of HVA and the elimination of HVA from the body. This article reviews many factors that help to determine the concentrations of HVA in body fluids and therefore must be considered in studies employing HVA as a possible index of central DA neuronal activity. The need for further methodological work is indicated to improve the use of body fluid HVA measurements in clinical research.

Dopamine in schizophrenia: a review and reconceptualization

The initial hypothesis that schizophrenia is a manifestation of hyperdopaminergia has recently been faulted. However, several new findings suggest that abnormal, although not necessarily excessive, dopamine activity is an important factor in schizophrenia. The authors discuss these findings and their implications. All published studies regarding dopamine and schizophrenia and all studies on the role of dopamine in cognition were reviewed. Attention has focused on post-mortem studies, positron emission tomography, neuroleptic drug actions, plasma levels of the dopamine metabolite homovanillic acid (HVA), and cerebral blood flow. Evidence, particularly from intracellular recording studies in animals and plasma HVA measurements, suggests that neuroleptics act by reducing dopamine activity in mesolimbic dopamine neurons. Post-mortem studies have shown high dopamine and HVA concentrations in various subcortical brain regions and greater than normal dopamine receptor densities in the brains of schizophrenic patients. On the other hand, the negative/deficit symptom complex of schizophrenia may be associated with low dopamine activity in the prefrontal cortex. Recent animal and human studies suggest that prefrontal dopamine neurons inhibit subcortical dopamine activity. The authors hypothesize that schizophrenia is characterized by abnormally low prefrontal dopamine activity (causing deficit symptoms) leading to excessive dopamine activity in mesolimbic dopamine neurons (causing positive symptoms). The possible co-occurrence of high and low dopamine activity in schizophrenia has implications for the conceptualization of dopamine's role in schizophrenia. It would explain the concurrent presence of negative and positive symptoms. This hypothesis is testable and has important implications for treatment of schizophrenia and schizophrenia spectrum disorders.

Iodine 131—Labeled Metaiodobenzylguanidine Scintigraphy and Biochemical Analyses in Suspected Pheochromocytoma

Detection of abnormal catecholamine levels and localization of tumor mass are important factors in the diagnosis and treatment of pheochromocytoma. Iodine 131-labeled metaiodobenzylguanidine scintigraphy was performed in 64 patients with suspected pheochromocytoma if their urinary catecholamine levels were borderline or elevated, or if the clinical suspicion for pheochromocytoma was high in spite of normal urinary catecholamine determinations. The 131I-metaiodobenzylguanidine scans were evaluated for abnormal localization of tracer. Twenty-four-hour urine collections were analyzed for vanillylmandelic acid, homovanillic acid, dopamine, epinephrine, and norepinephrine. Thirty of the 64 patients had pheochromocytomas. The 131I-metaiodobenzylguanidine scan had a sensitivity and a specificity of 88%. The 24-hour urine vanillylmandelic acid and norepinephrine measurements had the best sensitivity (97%), while the vanillylmandelic acid and homovanillic acid measurements had the best specificity (91%). In patients in whom the vanillylmandelic acid measurement and the 131I-metaiodobenzylguanidine scan were normal, no pheochromocytomas were found. In patients in whom the vanillylmandelic acid measurement and 131I-metaiodobenzylguanidine scan were abnormal, a pheochromocytoma was always present. The 131I-metaiodobenzylguanidine scan often documents the presence or absence of a pheochromocytoma and provides localization of the tumor in the preoperative evaluation of these patients.