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PubMed2001

Phaeochromocytoma: an unusual cause of hypertension in pregnancy.

A primiparous, full-term, 28-year-old woman underwent an emergency lower segment Caesarean section under epidural anaesthesia for failure to progress in the first stage. Despite an uneventful pregnancy and delivery, she developed a hypertensive crisis in the postoperative period complicated by acute pulmonary oedema requiring ventilation for 48 h in the intensive care unit. Intravenous magnesium sulphate infusions and hydralazine boluses were used to control the blood pressure, which was associated with clonus, hyperreflexia, tachycardia and profuse sweating. The patient made a good recovery. Later measurement of urinary catecholamines in the recovery phase showed greatly elevated levels of norepinephrine, dopamine and vanillyl mandelic acid. Further investigations included a normal abdominal computed tomography scan and a I-123 meta-iodo-benzyl-guanidine scintigraphy scan which revealed a 3- to 4-cm irregular tumour located at the level of the lower pole of the right kidney and further liver hot spots. Intravenous magnesium sulphate infusion proved successful in controlling hypertension caused by a phaeochromocytoma in the postpartum period.

Adrenal Gland Neoplasms↗
PubMed2001

Primary pheochromocytoma extending into the right atrium: report of a case and review of the literature.

Pheochromocytoma rarely extends locally into the vena cava or the right atrium. We report a case of malignant pheochromocytoma with growth into the inferior vena cava, extending into the right atrium, address clinical aspects of this tumour and review the literature on this malignancy. Pre-operative work-up of this tumour should include measurements of urinary vanillyl mandelic acid and cathecholamine excretion, MRI and spiral CT of the abdomen and thorax. After the diagnosis is made the patient should be treated with catecholamine alpha-receptor blockade and if necessary with subsequent beta-receptor blockade. An aggressive surgical approach is always warranted, even in cases with very large localized tumours, because surgery has been shown to lead to relief of symptoms and to prolong survival in cases otherwise deemed irresectable. The optimal surgical exposure is obtained via a transsternal midline thoraco-laparotomy. If feasible, a combination of cardiopulmonary bypass, hypothermia, cardiac arrest and exsanguination procedures should be used. In case of local of tumour remnants after surgery or distant metastases treatment options are secondary surgery, tumour embolization, or treatment with radioactive labelled drugs, including(131)I-MIBG.

Adrenal Gland Neoplasms↗
PubMed2003

Expression of PPAR-gamma is correlated with the clinical course of neuroblastoma.

BACKGROUND/PURPOSE: Neuroblastoma is a common pediatric tumor of the sympathetic nervous system. Unlike the ones found in older children, the tumors found in patients younger than one year of age often show spontaneous differentiation and regression. Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily is expressed in several human cancers. Recently, PPAR-gamma has been reported to be expressed in neuroblastoma, and the agonist of this receptor caused differentiation of neuroblastoma cells. METHODS: In this report we studied the expression of PPAR-gamma mRNA, using LightCycler in neuroblastoma samples diagnosed in 17 patients under the age of one year. RESULTS: Twelve samples showed PPAR-gamma mRNA expression. There was no significant difference in the PPAR-gamma mRNA expression based on age, histology, staging, and DNA ploidy. The PPAR-gamma mRNA expression level was significantly correlated with the change in urinary vanillyl mandelic acid (VMA). The neuroblastoma samples resected from patients who showed a decrease in their urinary VMA before the operation showed significantly higher PPAR-gamma expression than those from patients who showed an increase in their urinary VMA before the operation. CONCLUSIONS: PPAR-gamma may have played a role in the reduction of VMA and possibly in the regression of early-onset neuroblastoma.

Female↗
PubMed2000

New aspects in genotoxic risk assessment of styrene exposure--a working hypothesis.

Styrene is one of the most important plastic monomers worldwide. Styrene-7,8-oxide (SO), the major in-vivo metabolite of styrene, is classified as probably carcinogenic to humans and carcinogenic in rodents. Biological monitoring of exposure to styrene is usually carried out by determination of mandelic acid and phenylglyoxylic acid, the two main styrene metabolites in urine. SO binds covalently to human plasma protein and haemoglobin. The ability of SO to induce DNA adducts and DNA strand-breaks has been well documented. Recently in-vitro results showed that SO may disrupt the pre-existing oxidative status in white blood cells. This disruption would alter the balance between oxidants and antioxidants in cells. Styrene exposure can also result in oxidative DNA damage. A significant increase of 8-hydroxy-2;-deoxyguanosine (8-OHdG) has been found in white blood cells of styrene-exposed workers. According to these findings we propose a new hypothesis for the genotoxic risk assessment of styrene. Depletion of glutathione and increase in lipid peroxidation, similarity in the decrease of high molecular weight (HMW) DNA fragments after SO exposure compared to hydrogen peroxide (H(2)O(2)) exposure, oxidative DNA damage (increased amounts of 8-OHdG and an increased level of DNA strand-breaks) following styrene or SO exposure are due to oxidative stress which can be a result of the imbalance between oxidants and antioxidants. Formation of protein-, RNA- and DNA-adducts, changes in DNA repair capacity and styrene metabolism following styrene exposure could cause this imbalance between oxidants and antioxidants. Oxidative stress seems to be the basis for genotoxic risk assessment of styrene.

Humans↗
PubMed1993

Zollinger-Ellison syndrome and pheochromocytoma. Report of a case.

A 49-year-old woman was diagnosed in 1985 as having pheochromocytoma because of hypertension with high levels of plasma catecholamine concentration and 24-hour urine excretion of vanillyl-mandelic acid and metanephrine together with a right adrenal mass. The excised tumor cells had fine granular basophilic cytoplasm with argyrophilic granules by Grimelius' method. Four years later, she was diagnosed as having a duodenal bulb ulcer. Serum gastrin showed an abnormally high level of 1900 pg/ml. Abdominal echogram and computed tomography revealed a hypoechoic lesion in the pancreas and intrahepatic multiple tumors. A needle biopsy specimen of the liver tumor was compatible with the histology of metastatic islet cell tumor. A diagnosis of Zollinger-Ellison syndrome was made due to malignant gastrinoma with multiple liver metastases. The patient had no family history of endocrinological or neoplastic disorders. The present case indicates the possibility that pheochromocytoma and gastrinoma, that is, endocrine tumors characteristic of multiple endocrine neoplasia (MEN) I and MEN II, may be coincident even in a person without MEN. A continued awareness of previously rare or undescribed manifestations is important in patients with islet cell tumors or pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1989

Noradrenergic output and clinical response in depressed women during amitriptyline therapy.

The measurement of the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) in 59 unipolar depressed women before and during administration of 100 mg amitriptyline (AMT) i.m. daily for four weeks showed that the patients could be divided into high or low MHPG excretors. An analysis of the excretion course of MHPG and 3-methoxy-4-hydroxy mandelic acid during therapy showed, in most patients, a lower urinary excretion of both these noradrenaline (NA) metabolites in comparison with basal values. Therapy also decreased plasma noradrenaline concentrations and blood pressure values both at rest and on orthostatic challenge. Available evidence seems to suggest that AMT administration caused a lower overall noradrenergic output that might be partially responsible for a diminished sympathetic nervous activity. The authors were unable to confirm that the baseline MHPG level can predict the clinical response to antidepressant treatment and they found no significant correlations between changes in bio-chemical or physiological variables and drug plasma concentrations or clinical response. The possibility that depressed patients might be grouped according to their different NA metabolism needs to be validated in a larger patient sample.

Adult↗
PubMed1996

Active site-directed thrombin inhibitors: alpha-hydroxyacyl-prolyl-arginals, new orally active stable analogues of D-Phe-Pro-Arg-H.

D-alpha-Hydroxyacyl-prolyl-arginals, a new type of analogues of D-Phe-Pro-Arg-H (R1), have been prepared and evaluated. Unlike R1, whose terminal group is NH2, the new analogues with a terminal OH group are stable, as are the N-substituted derivatives of R1, that is, D-MePhe-Pro-Arg-H (R2), the highly potent and selective thrombin inhibitor, and Boc-D-Phe-Pro-Arg-H (R3), the much less favorable analogue. The most notable of the new analogues corresponds to the general formula D-Xaa-Pro-Arg-H, wherein Xaa means the acyl residue of mandelic acid (Man, 1), diphenyllactic acid (Dpl, 2), hexahydrophenyllactic acid (Hpl, 3), or hexahydromandelic acid (Hma, 4). In plasma clotting assays, 1 to 4 appeared to inhibit thrombin as well as some other clotting enzymes involved in thrombin generation, whereas R1 and R2 seemed to produce anticoagulation through inhibition of thrombin only. In the fibrin plate assay, 1 to 4 possessed even more moderate antifibrinolytic activities than R2. In in vivo evaluation in rats and rabbits, 2 to 4 proved to be potent anticoagulants/antithrombotics even on oral administration in a dose of 5 mg/kg. In view of these findings with the alpha-hydroxyacyl-prolyl-arginals, it is very likely that the less favorable biologic properties of Boc-D-Phe-Pro-Arg-H are due to the hydrophobicity and bulkiness of the terminal Boc-NH rather than its neutrality.

Administration, Oral↗
PubMed1993

[Recurrent paroxysmal neck swellings as the primary manifestation of a pheochromocytoma].

A 45-year-old female had been suffering for about 6 months almost daily from paroxysmal neck swellings with occasional difficulties in swallowing and from non-specific abdominal complaints. Hormone analyses, performed because of the marked blood pressure increase up to 210/120 mm Hg during such an attack, revealed an increase in vanillyl mandelic acid and epinephrine concentrations in the 24-hour urine. CT demonstrated a tumour of 4 x 5 x 5 cm size in the region of the right adrenal. The paroxysmal neck swellings and blood pressure increase could be reproduced by means of pressure applied over the tumour range with the ultrasound transducer. The tumour was extirpated and histology revealed a phaeochromocytoma. For more than one year now the patient has been free from complaints. To date, recurrent neck swellings have not been reported in association with a phaeochromocytoma. Possible causes may be an enhanced congestion of the deep neck vessels during paroxysmal blood pressure increase or an enhanced response by the adrenoreceptors of these vessels to the released catecholamines.

Adrenal Gland Neoplasms↗
PubMed1992

[The Shy-Drager syndrome].

For 15 years a now 70-year-old woman had been having occasional episodes of circulatory collapse which 7 years ago were diagnosed as being caused by severe idiopathic orthostatic hypotension. These episodes had recently become much more frequent and she was hardly able to be upright for more than one minute. In the Schellong test the blood pressure fell from 80/50 mm Hg when lying to 70/30 mm Hg on standing, the pulse rate remaining unchanged at 60/min. The standing test had to be abandoned after 90 seconds. Serum catecholamine concentrations (epinephrine 65 ng/l, norepinephrine 100 ng/l) did not rise on standing (epinephrine 25 ng/l, norepinephrine 105 ng/l). 24-hour urinary excretion of vanillyl mandelic acid was at the lower limit of normal (2.2 mg). The autonomic dysfunction of circulatory control suggested a Shy-Drager syndrome. Other signs of autonomic failure included gastroparesis, decreased tear and sweat secretion and transitory urinary incontinence. Symptomatic treatment with elastic stockings, fludrocortisone, etilefrine, dihydroergotamine, L-dopa, yohimbine and amezinium methylsulfate gave the patient greater mobility without achieving normal blood pressure responses.

Aged↗
PubMedDate not supplied

Evaluation of organic solvent ototoxicity by the upper limit of hearing.

To clarify the effects of organic solvents on hearing, we measured the upper limit of hearing in 93 male workers exposed to organic solvents in 7 factories that produced plastic buttons or baths. Medical examinations, environmental monitoring (i.e., concentration in breathing-zone air), and biological monitoring (i.e., concentration in urine) of the organic solvents were also done. Although the organic solvent concentrations in the environmental monitoring were lower than the occupational exposure limit, the upper limit of hearing was reduced in workers who were exposed for 5 y or more. This reduction was dose-dependent and was related to styrene concentrations in breathing-zone air and mandelic acid concentrations in urine. Even individuals who had normal medical examinations showed a reduced upper limit of hearing. The upper limit of hearing may serve as an early detection indicator of health effects in workers constantly exposed to styrene.

Acetone↗
PubMed1993

Evaluation of workload in air traffic controllers.

This study examined 20 air traffic controllers from the Rome Regional Air Control Centre for three successive work shifts: afternoon (13:00-20:00), morning (07:00-13:00) and night (20:00-07:00). The number of aircraft under control per hour was recorded as index of workload. Recordings involved subjective ratings (mood, physical fitness, fatigue) and objective measures (heart rate, vanillyl mandelic acid excretion, reaction times, critical flicker fusion, oral temperature). In addition, the subjects filled out questionnaires for personality traits (extroversion, neuroticis, anxiety) and behavioural characteristics (morningness, rigidity of sleeping habits, vigourness to overcome drowsiness). The volume of air traffic varied greatly with peaks during the day and low levels at night. Nevertheless, the heart rates of the group members showed quite constant levels in all the three shifts, irrespective of the workload. The same pattern appeared in the controllers' excretion of VMA, which remained high during both day and night shifts, regardless of the reduced workload. The subjective mood and physical fitness decreased similarly, while feelings of fatigue increased on all three shifts, particularly on the night shift. The circadian rhythm of the oral temperature showed a slight modification of the nocturnal depression during the night shift, caused by the state of awakeness and activity. However, the rhythm was not altered in its normal circadian phase, due to the fast shift rotation adopted. The psychophysiological responses were affected by personal characteristics, in particular morningness and ability to overcome drowsiness.

Adult↗
PubMed1979

Catecholamine activity and infectious disease episodes.

The profile of 3-hydroxy-4-methoxy mandelic acid (VMA) excretion was studied in relation to reported acute infectious disease episodes. Daily VMA excretion levels and symptom reports were analyzed for a group of 47 volunteers over a four-week period. Results showed a tendency for elevated VMA levels to occur with greater frequency within three days prior to the onset of symptoms. These findings are interpreted as suggesting that elevated levels of catecholamine activity may increase susceptibility to disease by interfering with the immune response, and in the presence of an agent lead to an infectious disease episode.

Adolescent↗
PubMed1999

Effect of styrene on monoamine oxidase B activity in rat brain.

Previous studies have indicated that workers exposed to styrene present a decreased activity of platelet monoamine oxidase B (MAO B), suggesting that this biochemical assay may represent a biomarker for styrene-induced neurotoxicity. This study was undertaken to determine whether exposure to styrene would cause changes in MAO B activity in the target organ--the brain. Groups of rats were exposed to styrene by inhalation at concentrations of 300 ppm for 4 wk or 50 ppm for 13 wk. Both treatments caused significant decreases of MAO B activity in several brain areas, while MAO A activity was not affected. Decreases in MAO B activity were also found in brainstem of rats given styrene (400 mg/kg) or styrene oxide (100 mg/kg) by i.p. injection for 2 wk. Styrene, styrene oxide, and other styrene metabolites (mandelic acid, phenylglyoxylic acid, and styrene glycol) had no direct inhibitory effect on brain MAO B activity when tested in vitro. These results indicate that exposure to low concentrations of styrene alters MAO B activity in rat brain, suggesting that the observed changes in human platelets may reflect alterations in the nervous system.

Administration, Inhalation↗
PubMed1999

Neuroblastoma in southern Africa: epidemiological features, prognostic factors and outcome.

We retrospectively analysed the epidemiological features and the importance of biochemical, histological and genetic parameters in predicting survival in 14 Namibian and 34 South African children treated for neuroblastoma (NB) from 1983 to 1997. Curative treatment consisted mainly of total (13%) or partial (44%) resection after chemotherapy (cyclophosphamide and doxorubicin x6 courses or carboplatin, etoposide, epirubicin and cyclophosphamide x6 courses). Localized radiotherapy with curative intent was given to 33% of patients. The male:female ratio was 0.9. The median age was 18 months (range 1-116) and was comparable in white, black and mixed ethnic patients. Primary disease was located in the abdomen (75%), thorax (15%), pelvis (5%) or elsewhere (5%). Evans stage distribution was: stage I, 2%; stage II, 19%; stage III, 21%; stage IV, 50%; and stage IVS, 8%. Stage III/IV disease was more common in black than in white children (p = 0.0001). Urinary vanillyl mandelic acid was elevated in 63% of those tested. Survival after 5-163 months' follow-up was 90% for stages I and II combined (median 2983, range 798-4661 days), 51% for stage III (median 367, range 61-5001 days), 6% for stage IV (median 227, range 20-4379 days) and 50% for stage IVS (median 532, range 54-1543 days). All seven children with para-spinal tumours survived. Individual factors associated with significantly poorer survival were elevated serum lactate dehydrogenase (p < 0.001), Joshi histological risk categorization adapted for age (p = 0.039), n-myc amplification (p = 0.006) and diploidy or tetraploidy (p = 0.006). All seven children with serum ferritin exceeding 149 ng/ml at the time of diagnosis died and survival was 33% in children with 1p deletion and 67% in those without, but the numbers were too small to achieve significance. These findings confirm the benefit of simple biochemical tests and histology in identifying those who are likely to respond favourably to conventional chemotherapy and surgery. Supportive genetic tests on formalin-fixed paraffin-embedded tumour tissue contributed to predicting outcome in 21 patients.

Abdominal Neoplasms↗
PubMed1976

The metabolites of catecholamines in urine of patients irradiated therapeutically.

The metabolites of catecholamines were determined in 24-hour urine samples of patients with genital carcinoma and treated by radio therapy. The patients were irradiated first with gamma-rays of radium and then with X-rays. The radium sources (80 mCi) were placed intracavitarily for 46 hours twice within 2 weeks. X-irradiation (800 R daily), applied 1 month after radium treatment, was delivered on four abdominal fields over 15 days. The quantities of excreted catecholamine metabolites during irradiation were compared with control values (obtained before irradiation) in the same patients. Gamma-irradiation provoked a significant increase in the excretion of 3-methoxy-4-hydroxy-mandelic acid, metadrenaline and normetadrenaline, as well as of homovanillic acid, whereas X-irradiation provoked only a significant increase in the excretion of free 3-methoxy-4-hydroxy-phenylglycol. The increased excretion might be explained: (1) in the case of radium application, by direct radiation-induced release of catecholamines from the peripheral symphathetic nerves; (2) in the case of X-irradiation, by putting in the motion the complex of early neuroendocrine reactions via irradiated adrenal medulla.

Adult↗
PubMed2001

Metabolism of the styrene metabolite 4-vinylphenol by rat and mouse liver and lung.

Styrene is a widely used chemical in the reinforced plastics industry and in polystyrene production. Its primary metabolic pathway to styrene oxide and then to styrene glycol, which is further metabolized to mandelic acid and phenylglyoxylic acid, has been well studied. However, a few studies have reported finding a minor metabolite, 4-vinylphenol (4-VP), in rat and human urine. The present studies sought to determine if the formation and metabolism of 4-VP in rat and mouse liver and lung preparations could be measured. When styrene was incubated with hepatic and pulmonary microsomal preparations, 4-VP formation could not be measured in these preparations. However, considerable 4-VP metabolizing activity, as determined by the loss of 4-VP, was observed in both mouse and rat liver and lung microsomal preparations. 4-Vinylphenol metabolizing activity in mouse liver microsomes was three times greater than that in rat liver microsomes, and activity in mouse lung microsomes was eight times greater than that in rat lung microsomes. This activity was completely absent in the absence of NADPH. Studies with cytochrome P-450 inhibitors indicated the involvement of CYP2E1 and CYP2F2. Induction of CYP2E1 by pyridine resulted in an increase in 4-VP metabolism by mouse hepatic microsomes but not by pulmonary microsomes. The metabolite(s) formed as a result of this oxidative pathway remain to be identified. In additional studies, glutathione conjugation appeared to be involved in 4-VP metabolism with the highest activity being in mouse lung, with or without the addition of NADPH.

Analysis of Variance↗
PubMed2000

Aggression in boat builders: a search for altered mood states in boat builders exposed to styrene.

Published reviews and industrywide anecdotal reports have suggested an association between exposure to some volatile organic compounds (VOCs) and altered mood states. In this paper we report a unique study of boat-builders exposed to styrene. Two hundred and thirteen employees exposed to solvents and 144 who were not exposed completed questionnaires related to mood states. Additionally, for 23 of the 213 employees, the air concentrations of styrene were measured at their workplaces, and urinary concentrations of mandelic acid (a metabolite of styrene) were determined in order to assess biological exposure. Special features of this study included the use of the Prolife of Mood States (POMS) questionnaire and the availability of sound historical data. A weak association is demonstrated between styrene exposure and aggression/hostility. That this is found to be most marked in the earliest years of exposure suggests that selection characteristics might be a more important association than solvent exposure.

Adult↗
PubMed1984

Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding.

This study was performed to investigate the mechanism whereby immediate enteral feeding after burn injury reduces postburn hypermetabolism and hypercatabolism. Fifty-seven burned guinea pigs (30% TBSA) were divided into three groups: A (N = 19), given 175 kcal/kg/day beginning 2 hours after burn; B (N = 20), given 175 kcal/kg/day with an initial 72-hour adaptation period; and C (N = 18), given 200 kcal/kg/day with the same adaptation period as B. Resting metabolic expenditure (RME) on PBD 13 was lowest in group A (109% of preburn level), compared with group B (144%, p less than 0.001) and group C (137%, p less than 0.01). On PBD 1, group A had the greatest jejunal mucosal weight and thickness (p less than 0.001), and mucosal weight had negative correlations with plasma cortisol (r = 0.829, p less than 0.001) and glucagon (r = 0.888, p less than 0.001). Two weeks after burn, urinary vanillyl mandelic acid (VMA) excretion, plasma cortisol, and glucagon were lowest in group A (p less than 0.05 to p less than 0.01). These hormones also significantly correlated with RME (p less than 0.01 to p less than 0.001). These findings suggest that immediate postburn enteral feeding can prevent hypermetabolism via preservation of gut mucosal integrity and prevention of excessive secretion of catabolic hormones.

Animals↗