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Utility of follow-up studies using meta-[123 I]iodobenzylguanidine scintigraphy for detecting recurrent neuroblastoma.

Neuroblastomas sometimes recur after the initial disappearance of the tumour. We evaluated the utility of meta-[123I]iodobenzylguanidine (123I-MIBG) scintigraphy for the detection of recurrent neuroblastomas by comparing with the measurement of biochemical markers and clinical findings. Forty patients who had received treatment for neuroblastomas were included in the study. After the disappearance of the initial tumours, periodic measurements of urinary vanillyl mandelic acid, homovanillic acid and serum neuron specific enolase values, and an 123I-MIBG scintigraphy were performed. Whenever an abnormal finding was observed, other appropriate examinations and/or follow-up examinations were performed to elucidate the true state of the patient. Eleven recurrent episodes in eight patients were observed. Most of them occurred in the bone marrow or bone. Corresponding symptoms were observed in only two episodes; the other episodes were asymptomatic, and discovered by the periodic examinations. 123I-MIBG scintigrams visualized the recurrent tumours in 10 (91%) episodes. Elevated tumour markers were observed in only three episodes. 123I-MIBG scintigrams visualized most of the recurrent tumours, unless they were accompanied by any symptoms or elevations in biochemical tumour markers. Periodic examinations with 123I-MIBG scintigraphy appears to be a useful technique for the detection of the recurrences.

3-Iodobenzylguanidine↗

Multiple indicators of stress in an 'active' job--cardiothoracic surgery.

Eight members of a cardiac surgery team were monitored for a variety of stress indicators. These included self-reports of felt stress, observations of behavior related to ECG activity, and measurements of urinary cortisol and 3-methoxy-4-hydroxy-mandelic acid (VMA). Observations were made on 12 separate days spread over a 3-month period. Results indicate moderate to low levels of perceived stress with high levels of satisfaction and high levels of support. ECG data showed wide individual variation; heart rates even during operations were not excessively high (mean, 100 beats per minute). VMA levels were within the normal range. Cortisol levels were above the normal range on 72% of measurements and mean levels were positively related to length of experience. Days when self-perceived stress was reported were associated with higher levels of cortisol but not of VMA. The study failed to support predictions about responses to "active" jobs derived from Karasek's job-strain model.

Cardiac Surgical Procedures↗

Management of urinary tract infections: historical perspective and current strategies: Part 1--Before antibiotics.

PURPOSE: Urinary tract infections (UTIs) have plagued mankind long before bacteria were recognized as the causative agents of disease and before urology became an established medical specialty. To our knowledge a comprehensive review of the recorded medical history of UTI from its first description in ancient Egyptian papyri through today has not been attempted until now. MATERIALS AND METHODS: Numerous resources were used to collect the information described in this review. Older textbooks from the school of medicine library at our institution were used to collect information on UTI in ancient times. Medical texts from the 19th century contains information regarding the treatment of UTI during that era. Early volumes of the Journal of Urology from the beginning of the 20th century are rich with information on the first attempts at chemotherapy for UTI. MEDLINE searches were used to collect appropriate information after 1969. RESULTS: The Ebers papyrus from ancient Egypt recommended herbal treatments to ameliorate urinary symptoms without providing insight into pathological mechanisms. Hippocrates believed that disease was caused by disharmony of the 4 humors and accordingly diagnosed urinary disorders. Roman medicine further expanded the conservative approach (bed rest, diet, narcotics and herbs) advocated by Greek physicians, while also improving invasive techniques (surgical lithotomy for stones and catheterization for retention). The Arabian physician Aetius refined uroscopy and created a detailed classification and interpretation of urinary disease based on this technique. During the Middle Ages no major advances occurred, although existing therapies were refined and treatments for gonococcal urethritis were well described. The early 19th century provided vivid and detailed descriptions of UTIs without the knowledge that they were caused by microorganisms. Management included hospitalization, bed rest, attention to diet, plasters, narcotics, herbal enemas and douches, judicious bleeding (direct bleeding, cupping and leeches), and surgery for stones, abscess and retention. The discovery of microorganisms as the etiological agents of infectious diseases in general and inflammation associated with urinary diseases in particular provided an impetus for physicians critically to examine management approaches and develop evidence based strategies for UTI treatment. Various antibacterial agents, such as hexamine, mercurochrome and others (hexylresorcinol, methylene blue, pyridium, acriflavin and mandelic acid), showed promise in laboratory studies but their efficacy in clinical investigations was disappointing. CONCLUSIONS: Treatments for UTI until the discovery of antibiotics were largely palliative because the bacterial origin of UTI was not recognized and no specific antimicrobial therapies were available.

China↗

Catecholamines levels and parotid secretion in children with chronic atopic dermatitis.

The purpose of this study was to evaluate the in vivo state of both branches of the autonomic nervous system in children with chronic atopic dermatitis. In 15 patients, age 4 to 11, the following parameters were analyzed: (1) basal plasma levels of epinephrine, norepinephrine, and dopamine; (2) poststimulation (standing and i.v. furosemide administration); (3) basal urinary excretion of epinephrine, norepinephrine, and vainillin mandelic acid; (4) 30 min postfurosemide administration; (5) parotid secretory response to intraoral 0.1 m citric acid: flow rate, saliva pH, and concentrations of bicarbonate, chlorides, inorganic phosphates, total protein, and amylase activity. No differences in plasma and urinary basal levels of the catecholamines were observed. In response to standing, plasma norepinephrine from atopic children showed a greater increase than that seen in normal healthy children. From the salivary factors studied, no differences were found in parotid flow-rate, bicarbonates, chlorides, and inorganic phosphates. Protein concentration as well as amylase activity were significantly decreased in children with atopic dermatitis. These findings suggest that in atopic dermatitis, the beta-sympathetic mediated responses are impaired; on the other hand, parasympathetic mediated responses remain preserved.

Catecholamines↗

Studies on the effects of propanolol on plasma catecholamine levels in patients with essential hypertension.

The influence of the beta receptor blocking agent propranolol on plasma catecholamine concentrations was studied in eight patients with essential hypertension. The study was of single blind crossover design. Propranolol given in oral doses ranging from 60 to 240 mg daily for a period of 3 weeks decreased blood pressure and heart rate. The beta-adrenergic blocking agent caused plasma catecholamine levels to increase both at rest and during bicycle exercise. Chromatographical analysis showed that concentrations of noradrenaline as well as of adrenaline rose during treatment with propranolol. However, dopamine-beta-hydroxylase activity in plasma was not altered. Furthermore, the urinary excretion of noradrenaline, adrenaline and 4-hydroxy-3-methoxy mandelic acid did not change during beta receptor blockade. The results are compatible with the assumption that antihypertensive doses of propranolol by decreasing cardiac output cause an activation of the sympatho-adrenal system.

Adult↗

A case of ischemic colitis associated with pheochromocytoma.

A 40-year-old woman was admitted because of abdominal pain and diarrhea. She sometimes experienced paroxysmal hypertension, sweating, headache, and palpitation. Sigmoidoscopic findings showed well-demarcated diffuse mucosal edema, hyperemia, and easy touch bleeding from distal descending colon up to the splenic flexure area. Barium x-ray showed loss of haustral marking, thumb printing appearance, and diffuse luminal stenosis in the transverse, descending, and sigmoid colon. On the abdominal computed tomogram, a 3.8-cm sized well-enhanced right adrenal mass was incidentally found. Twenty-four hour urinary excretion of vanillyl mandelic acid, norepinephrine, and normetanephrine were increased. Iodine131 metaiodobenzylguanidine scan showed hot uptake on the right adrenal gland compatible with pheochromocytoma. Exploratory laparotomy was done under the impression of ischemic colitis associated with pheochromocytoma. Adrenalectomy and resection of the stenotic left colon were performed. After surgery, pain subsided, blood pressure fell gradually, blood sugar and catecholamine level became normal, and bowel habit returned to normal.

Adrenal Gland Neoplasms↗

A study of urinary excretion of biogenic amine metabolites in epilepsy.

Urinary total catecholamines, their metabolites, and a metabolite of serotonin have been investigated in 20 patients with epilepsy, and in 10 controls. The levels of total catecholamines, vanillyl mandelic acid and 5-hydroxyindole acetic acid in epileptics were not significantly different from the controls. However, the mean 3-methoxy-4-hydroxyphenylglycol, excretion in cases of epilepsy was significantly increased as compared to the control group. It is concluded that a central catecholaminergic disturbance is involved in the pathogenesis of epilepsy.

Adolescent↗

Optimization and application of the head space liver S9 equilibration technique for metabolic studies of organic solvents.

A head space liver S9 vial equilibration technique for qualitative and quantitative metabolism of volatile organic solvents in vitro is described and investigated for optimal experimental conditions with toluene and n-hexane as model substrates. The method was also used for studying the metabolic interaction between acetone and styrene. NADP+ was a critical cofactor in the system as concentrations above 2.5 mM resulted in inhibition of metabolism. Induction of cytochrome P450 by phenobarbital did not alter the observed cofactor dependency, and addition of vehicles such as rat blood did not enhance metabolism. Acetone-induced liver S9 increased the primary oxidation of styrene and also the formation of styrene oxide, but not significantly that of mandelic acid. Acetone as such had no effect on the metabolic elimination of styrene, indicating that the interaction is mainly on the level of enzyme induction occurring after long-term exposure to acetone. As earlier reports on styrene metabolism in vivo has not been able to detect styrene oxide in toxicokinetic studies with a sufficient degree of accuracy, the head space liver S9 vial equilibration technique may offer a fast and sensitive tool for screening of metabolic interactions between organic solvents when optimized for metabolic activity.

Acetone↗

Patterns of endocrine reactivity in patients with recent myocardial infarction. Clinical and biochemical correlations: trial of endocrine therapy.

The following endocrine function parameters were studied serially in a group of 10 patients with recent myocardial infarction: blood and urinary levels of epinephrine and norepinephrine, urinary excretion of vanillyl-mandelic acid; protein-bound iodine, Hamolsky test (Hamolsky, Stein, and Freedberg, 1957); blood insulin; 24-hour urinary excretion of 17-hydroxycorticoids, sodium, and potassium. The acute phase of myocardial infarction, especially in those patients with a severe clinical course (rhythm disturbances, coronary insufficiency, circulatory failure), was associated with disturbed endocrine reactivity. The most frequent and the earliest feature was the increased level of the 24-hour urinary excretion of epinephrine, combined with a pronounced decrease in blood insulin level. Later in the course of the disease, as the adrenergic reactivity returned to normal, there was an increase in blood insulin to normal levels. In 3 patients with severe clinical symptoms of acute myocardial infarction, there were, in addition to the increased 24-hour urinary excretion of catecholamines, a decreased blood insulin, higher than normal levels of protein-bound iodine, and of the Hamolsky test. One of these patients developed hypoadrenia. It is possible that the abnormal endocrine reactions accelerate the catabolic processes within cardiac tissue (catecholamines, thyroid hormones), especially when there is a possible functional deficiency of hormones, occurring as a general adaptation reaction to stress (cortisol, insulin). The disturbances that follow may be dangerous for the patient.

17-Hydroxycorticosteroids↗

Biochemical diagnosis of phaeochromocytoma: two instructive case reports.

The biochemical features of two patients with phaeochromocytomas illustrate the inadvisability of depending on a single group of analytes for the diagnosis. The first case presented as a surgical emergency with retroperitoneal haemorrhage. Biochemical diagnosis was difficult since total 24 hour urinary free catecholamine excretion was within normal limits in two out of three samples, and only marginally raised in the third with an atypical preponderance of adrenaline. Plasma catecholamine concentrations were also normal. But urinary excretion of the catecholamine metabolites, metadrenaline and 4-hydroxy-3-methoxy mandelic acid (HMMA), was consistently raised. In contrast, the second patient presenting with headache and labile hypertension showed normal metabolite excretion in the face of grossly increased free noradrenaline excretion and raised plasma noradrenaline concentrations. It is therefore recommend that, as well as urinary free catecholamines, one group of their main metabolites, the 3-methoxy amines (normetadrenaline and metadrenaline) or HMMA, should routinely be measured whenever a phaeochromocytoma is suspected.

Adrenal Gland Neoplasms↗

Clinical and neurobehavioural study of the acute and chronic neurotoxicity of styrene.

A cross sectional field study of workers exposed to styrene was performed to evaluate possible acute and chronic neurotoxic effects. A total of 36 workers of four companies handling polyester resin materials for one to 16 years (median: 7 years) and two control groups were each examined on a Monday. The control group 1 (formed to compare acute effects) consisted of 20 men from two companies with no exposure to neurotoxic chemicals. To compare chronic effects, a second control group was formed by "one to one matching" with respect to age, socioeconomic status, and pre-exposure intelligence level. Ambient air monitoring using active sampling (short time) and passive samplers (long time) showed styrene in air concentrations as follows: range 3-251 ppm (median: 18 ppm) and concentrations 140-600 ppm during lamination of the inside of boats. For biological monitoring the results were as follows (postshift samples: range/median): styrene in blood: 5-482 micrograms/dl (39 micrograms/dl), mandelic acid urine: 0.01-3.64 g/l (0.21 g/l), and phenylglyoxylic acid urine: 0.01-0.87 g/l (0.19 g/l). The clinical examination found no signs or symptoms of peripheral neuropathy or encephalopathy. The principal work related health complaints were acute, reversible irritation of the eyes that occurred after exposure to styrene concentrations of 200 ppm or more. The neurobehavioural tests showed no significant differences in acute effects (p greater than 0.05) between the two groups or between preshift and postshift testing. Nor were there any significant differences in the relevant neurobehavioural variables between the styrene workers and the controls. It is concluded that occupational exposure to styrene concentrations in air up to 100 ppm causes no adverse acute or chronic effects on the central nervous system.

Acute Disease↗

Subclinical impairment of colour vision among workers exposed to styrene.

The effects of exposure to styrene were studied among 60 men aged 20 to 56 (mean 29.5) employed in shipbuilding. Exposure was due to the handling of glass reinforced polyester materials. The study was cross sectional and the workers were compared with a control group matched for age, social and occupational state, and ethnic origin. During the study, the mean atmospheric exposure to styrene was 24.3 ppm. Mean urinary elimination was 230 mg/g creatinine for mandelic acid and 57.4 mg/g creatinine for phenylglyoxylic acid. The Farnsworth 100 hue test showed no significant differences between the exposed and control groups for error scores. A significant difference was found, however, for the number of subjects with errors axis in the red-green, or blue-yellow ranges, or both, which was larger among the exposed workers (32/60 v 20/60 for the controls (p < 0.05)). Psychometric tests were also conducted, using the World Health Organisation (WHO) neurobehavioural core test battery. Of the seven tests it included, anomalies were only found for the aiming test. These results suggest that exposure to moderate styrene concentrations of the order of 25 ppm can lead to impairment of colour vision.

Adult↗

Increased urinary excretion of catecholamines and their metabolites in streptozotocin diabetic rat.

An attempt has been made to measure changes in the endogenous noradrenaline contents of hearts and brains in rats made diabetic by intravenous administration of streptozotocin. There was no significant change in the endogenous noadrenaline content in the hearts and brains of these diabetic rats. However, all the diabetic animals showed increased excretion of adrenaline, noradrenaline and 3-methoxy-4-hydroxy mandelic acid. This increased excretion was seen as early as 3 days after streptozotocin injections. The rate of disappearance of (3H)-noradrenaline from the heart was significantly higher in these diabetic rats when compared to age-matched controls. It is concluded that there is an increased sympathetic activity in these diabetic animals which is reflected by increased disappearance of (3H)-noradrenaline and increased urinary catecholamine excretion.

Animals↗

Amniotic fluid catecholamine metabolites in maternal smoking.

The concentration of dopamine (DA), norepinephrine (NE), and its metabolites 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG) and vanillyl mandelic acid (VMA), and prostaglandins E2, and F2a in amniotic fluid were measured at labor (1-3 cm of cervical dilatation), in uncomplicated and complicated pregnancies. The amniotic fluid concentration (mean +/- SD) of MHPG in maternal smoking (S) (30.6 +/- 11.9 nmol.mg creatinine-1) and intrauterine growth retardation (IUGR) (36.7 +/- 15.2 nmol.mg creatinine-1) groups is significantly higher than in uncomplicated pregnancies (C) (22.9 +/- 8.8 nmol.mg creatinine-1), or diabetes mellitus groups (D) (26.1 +/- 10.9 nmol.mg creatinine-1) groups; VMA presents similar differences between groups S (145.8 +/- 84.4 nmol.mg creatinine-1) and IUGR (173.0 +/- 135.4 nmol.mg creatinine-1) higher than C (58.3 +/- 26.1 nmol.mg creatinine-1) and D (76.8 +/- 49.0 nmol.mg creatinine-1) groups. NE levels differ between groups in a similar way, but DA does not present significant differences between groups. Prostaglandin levels are higher in the S than in the C group. Nicotine action and/or hypoxia are proposed as a possible cause of NE, MHPG, and VMA rise in amniotic fluid of S, and IUGR versus C or D groups.

Amniotic Fluid↗

Routine laboratory investigation of urinary catecholamine metabolites in sick children.

Simple and rapid thin-layer chromatographic methods have been used to investigate the catecholamine metabolites present in the urine of sick children. A semi-quantitative method for 4-hydroxy-3-methoxy-mandelic acid (HMMA) has been devised and compared with the quantitative spectrophotometric procedure. The methods have been performed on both normal subjects and children with catecholamine-secreting tumours, without dietary restriction, and have led to a 50% reduction in the number of samples requiring laborious quantitative determination of HMMA excretion.

Catecholamines↗