Traumatic stress, mental health, and quality of life in adolescents with esophageal atresia.

INTRODUCTION: We aimed to investigate QoL in EA patients in relation to comparison groups and to clinical factors including experienced traumatic stress. MATERIAL AND METHODS: Adolescents with EA in Norway born between 1996 and 2002 were included. Clinical assessment and patient's characteristics were collected. Quality of life (PedsQL), traumatic stress (IES-13) and mental health (SDQ-20) were compared to groups of healthy controls, children with acute lymphoblastic leukemia (ALL) and kidney transplanted children (TX). RESULTS: 68 EA adolescents participated. Total scores for PedsQL were not different from the healthy group and ALL patients, but significantly better than the TX patients. The subscale for physical performance was significantly lower than in healthy adolescents, and nine (17%) patients had scores ≤70 indicating reduced health status. Five EA adolescents (12%) had mental health scores suggesting a psychiatric disorder, and six (9%) reported high traumatic stress scores with a significant correlation to days on ventilator in the neonatal period. The strongest predictors for quality of life among EA adolescents were self-reported mental health, posttraumatic stress and GERD symptoms. CONCLUSION: Scores for Quality of life in the EA group are good except for subscale for physical performance. Symptoms of posttraumatic stress, mental strain and gastroesophageal reflux are predictors of reduced QoL.

Prenatal extravasation of urine seems to preserve renal function in boys with posterior urethral valves.

INTRODUCTION: A posterior urethral valve (PUV) may lead to extravasation of urine, resulting in prenatal ascites and/or perirenal urinoma. Extravasation has been presumed to act as a pop-off mechanism, preserving renal function, but previous reports addressing this presumption have been inconclusive. AIM OF STUDY: The present study compares renal function in patients with PUV with and without extravasation. MATERIAL AND METHODS: Sixty boys with a confirmed diagnosis of PUV as neonates (gestational age [GA]<44 weeks) throughout 2001-2016 were included. Clinical data were collected from medical records. Renal function was assessed by nadir plasma creatinine, creatinine at the last follow-up, and glomerular filtration rate (GFR) at the last follow-up. The GFR was estimated using the Schwartz formula. Renal function was classified according to the kidney disease: improving global outcomes (KDIGO) guidelines' grades of chronic kidney disease (CKD). Glomerular filtration rate > 90 ml/min/1.73m2 at the last follow-up was classified as normal renal function. RESULTS: Twelve patients (20%) had ascites and/or urinoma, and 48 (80%) did not. GA and birth weight were not different in patients with and without extravasation. PUV was suspected from prenatal ultrasound findings in 66.7% of the patients in both groups. Median nadir creatinine was 21 (range, 11-33) µmol/L in boys with ascites/urinoma, and all values were within the age-adjusted reference values. Nadir creatinine was 23 (14-199) µmol/L in boys without extravasation, and it was above the normal range in 14 boys. The incidence of elevated nadir creatinine was significantly different in the two groups (p < 0.025). One of the 12 patients with extravasation developed chronic renal failure (CKD 3). In the group of 48 patients without extravasation, 20 (42%) had chronic renal failure grade 2-5, and among these, 5 patients have had a renal transplant (CKD grade 5). The prevalence of CKD grade 2-5 was statistically different in the two groups (p = 0.03). These findings are presented in the summary figure. CONCLUSION: Extravasation of urine was found in 12 of 60 (20%) boys with PUV. These patients had significantly lower prevalence of CKD at the last follow-up than patients without extravasation. This finding is important in prenatal counseling. It also indicates that prenatal decompression of the bladder and upper tract is beneficial in patients with PUV, which is relevant to the discussion of prenatal intervention in these fetuses.

Cardiovascular risk factors in epilepsy patients taking levetiracetam, carbamazepine or lamotrigine.

OBJECTIVES: The aim of the study was to investigate risk factors for cardiovascular disease in patients with epilepsy using the new antiepileptic drug levetiracetam (LEV), compared with patients taking carbamazepine (CBZ) or lamotrigine (LTG). METHODS: Two hundred and twelve patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 52), CBZ (n = 87) or LTG (n = 73) monotherapy for at least 6 months. Total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured. Smoking, drinking habits and physical activity were recorded and body mass index (BMI) was calculated. RESULTS: Neither LEV nor LTG altered TC, LDL or HDL. Both men and women using CBZ had higher TC, HDL and LDL than controls. LDL/HDL and TC/HDL ratios were unchanged. Women on CBZ and LTG had a greater BMI when compared with the control group. Patients with epilepsy recorded less physical activity and lower alcohol use than the controls. CONCLUSIONS: Neither LEV nor LTG affected blood lipid levels, while patients treated with CBZ have higher cholesterol, HDL and LDL than controls. The patients were less physically active, and women on CBZ and LTG had higher BMI.

Increased levels of C-reactive protein and interleukin-6 in hyperhomocysteinemic subjects.

OBJECTIVE: Elevated plasma homocysteine concentration is considered to be an independent risk factor for cardiovascular disease. However, the mechanisms by which hyperhomocysteinemia are related to vascular disease are unclear. High-sensitivity C-reactive protein (CRP), a marker of inflammation, has been reported to be an independent predictor of future myocardial infarction among clinically healthy individuals. Interleukin (IL)-6 is a regulator of CRP and has a key role in initiation of inflammation. The aim of this study was to investigate whether individuals with increased plasma homocysteine concentrations have altered levels of serum CRP and IL-6. MATERIAL AND METHODS: Serum concentrations of CRP and IL-6 were measured in 39 individuals with hyperhomocysteinemia and in 39 control subjects matched for gender, age and body mass index (BMI). In addition, the inflammatory effect of IL-6 on peripheral blood mononuclear cells was measured. RESULTS: Compared to controls, hyperhomocysteinemic subjects have elevated serum levels of CRP and IL-6 (p < or =0.001 and p < 0.005, respectively). Importantly, this raised level of IL-6 was also seen in hyperhomocysteinemic individuals without accompanying hypercholesterolemia or cardiovascular disease. IL-6 increased the release of monocyte chemoattractant protein-1 from peripheral blood mononuclear cells, with particularly enhancing effects in cells from patients with hyperhomocysteinemia. CONCLUSIONS: These data suggest that enhanced inflammation may be associated with homocysteine-related cardiovascular disease, possibly involving IL-6-related mechanisms.

Diverse effects of P-glycoprotein inhibitory agents on human leukemia cells expressing the multidrug resistance protein (MRP).

UNLABELLED: Multidrug resistance (MDR) to cancer chemotherapy is frequently associated with decreased drug accumulation in cancer cells due to drug expulsion by multidrug transporters such as P-glycoprotein (Pgp) and multidrug resistance protein (MRP). The novel resistance modifying agents PSC 833, 280-446, and LY 335979 are primarily targeted at inhibition of Pgp, and their MRP inhibitory potential is largely unknown. OBJECTIVE: In the present study we addressed the effect of these agents on MRP-derived drug resistance. MATERIALS: Drug-resistant human leukemia cells with Pgp+/MRP- (KG1a/200, K562/150) and Pgp-/MRP+ (HL60/130) phenotypes were maintained in suspension cultures for experimental studies of drug accumulation and drug sensitization by Pgp inhibitors. METHODS: Intracellular accumulation of the fluorescent anthracycline daunorubicin was measured by flow cytometry and fluorescence detection. Daunorubicin dose-response curves were generated by non-linear regression of electronically measured cell counts of 72- - 96-h cultures. The half-maximal growth inhibitory dose (GI50) was used as measure of growth inhibition. RESULTS: All MDR phenotypes studied exercised significant resistance to daunorubicin. PSC 833, 280-446 and LY335979 were equal in sensitizing Pgp+/MRP- cells to daunorubicin-induced growth inhibition (p < 0.0001). The Pgp-/MRP+ cells responded to PSC 833 and 280-446 by increased accumulation of daunorubicin (p = 0.0022 and p = 0.0005, respectively) and sensitization to the drug (p = 0.0009 and p = 0.0007, respectively). Conversely, LY335979 did not affect accumulation of daunorubicin in Pgp-/MRP+ cells nor sensitize these cells to daunorubicin. CONCLUSION: Pgp inhibitory agents have differential effects on MRP-derived drug resistance which could be exploited in treatment of multidrug resistance in cancer patients.

The endocrine transition around menopause--a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women.

OBJECTIVE: The purpose of this study was to investigate the hormonal changes during the menopausal transition in a non-clinical population. METHODS: Fifty-nine healthy Norwegian women participated in a five year prospective longitudinal study during the transition from pre- to post-menopause, starting one to four years before menopause, and ending one to four years postmenopausal. None of these women were given hormone replacement therapy (HRT). Blood samples were collected every 12 months and luteinizing hormone (LH), follicle stimulating hormone (FSH), steroid hormone binding globuline (SHBG), prolactin (PRL), estradiol (E2), estrone (E1), testosterone, androstendione, dehydroepiandrostendione-sulphate (DHEA-S), and thyroid stimulating hormone (TSH) were analyzed. RESULTS: The serum levels of FSH and LH, E2 and E1 profile essentially confirmed previous data obtained in cross-sectional studies. A continuous increase in serum FSH and LH and a concomitant fall in E2 and E1 were observed in all women before menopause and in the two postmenopausal years. Both androstendione and testosterone showed a decline three years before menopause. After the menopause, however, there were fluctuations in the testosterone levels. Androstendione correlated positively with both E2 and E1 and testosterone postmenopausally. Body mass index (BMI) did correlate with testosterone, but not with androstendione. BMI correlated negatively with SHBG. No correlation was found between BMI and E2, E1, FSH and LH. CONCLUSION: This longitudinal prospective study of hormonal changes during the transition from pre- to postmenopause indicates that not only estrogen hormonal changes, but androgen hormonal changes as well, precedes the menopause by several years.

Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis.

The serum level of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D], the biologically most potent metabolite of vitamin D, is tightly regulated within narrow limits in human healthy adults. 1,25-(OH)2D deficiency is rare and is associated with disturbances in calcium and bone metabolism. We have previously reported a marked decrease in serum levels of 1,25-(OH)2D in human immunodeficiency virus (HIV)-infected patients. The present study was designed to further examine the causes and consequences of severe 1,25-(OH)2D deficiency in these patients. The design was a prospective cohort study. Fifty-four HIV-infected patients clinically classified according to the revised criteria from Centers for Disease Control and Prevention and healthy controls were studied. Parameters related to vitamin D and calcium metabolism as well as immunological and nutritional status were determined. Twenty-nine of the patients (54%) had serum levels of 1,25-(OH)2D below the lower reference limit, and 18 of these had undetectable levels. In contrast, HIV-infected patients had normal serum levels of 25-hydroxyvitamin D and vitamin D-binding protein. HIV-infected patients as a group had modestly depressed serum calcium and PTH levels. There were, however, no correlations between these parameters and serum levels of 1,25-(OH)2D. There were no differences in serum calcium or PTH levels or nutritional status when patients with severe 1,25-(OH)2D deficiency were compared to other patients, but patients with undetectable 1,25-(OH)2D had significantly elevated serum phosphate levels. Furthermore, patients with undetectable 1,25-(OH)2D levels were characterized by advanced clinical HIV infection, low CD4+ lymphocyte counts, and high serum levels of tumor necrosis factor-alpha (TNFalpha). We conclude that inadequate 1alpha-hydroxylation of 25-hydroxyvitamin D seems to be the most likely cause of 1,25-(OH)2D deficiency in HIV-infected patients, possibly induced by an inhibitory effect of TNFalpha. The low 1,25-(OH)2D and high TNFalpha levels observed may impair the immune response in HIV-infected patients both independently and in combination and may represent an important feature of the pathogenesis of HIV-related immunodeficiency. Markedly depressed 1,25-(OH)2D serum levels are also present in certain other disorders characterized by immunological hyperactivity. Thus, the findings in the present study may not only represent a previously unrecognized immune-mediated mechanism for induction of 1,25-(OH)2D deficiency in human disease, but may also reflect the importance of adequate serum levels of 1,25-(OH)2D for satisfactory performance of the immune system in man.

Anorectal anomalies: anorectal manometric function and anal endosonography in relation to functional outcome.

To assess the relation between continence and the manometric and endosonographic state of the anorectal segment after surgery for anorectal anomalies (ARA), 33 adolescents operated upon for ARA and 14 controls were examined. Seventeen patients had low and 16 intermediate or high ARA. Fecal continence was recorded, and anal canal manometry was performed by microtransducer. The sphincter muscle complex and its relation to the anal opening was visualized by anal endosonography (ES). Ten patients had perfect continence, 10 had staining, and 13 had soiling. The anal canal resting and squeeze pressures were significantly different in all three groups, and continence function was significantly correlated to anal canal pressures. By anal ES, the internal (IAS) and the external anal sphincters (EAS) were identified with various amounts of scar tissue in all patients. In patients with high or intermediate anomalies the IAS was missing in the lower part of the anal canal, and abundant scar tissue was identified in the EAS in all patients. In patients with good continence function, the EAS was better preserved than in patients with major incontinence. The position of the anus in the EAS muscle complex was assessed, and varying degrees of eccentrically placed anal canals were identified. Continence function after surgery for ARA is thus correlated to anal canal pressures and ES images. ES, which is painless and suitable for use in children, is a valuable tool for assessing perianal structures, and the findings may serve as a helpful guide for corrective surgery.

Evaluation of an enzymatic immunoassay for free thyroxine determination in canine serum.

Free thyroxine (FT4) and cholesterol were measured in 400 dogs with either suspected hypothyroidism or dermatological signs such that hypothyroidism needed to be ruled out. Hypothyroidism was diagnosed in 68 dogs from the history, physical examination and stated lower reference limit (< 7 pmol/L) for FT4 in euthryoid dogs. Dogs with FT4 concentrations in the range 6-9 pmol/L were finally categorized as hypo- or euthyroid either on the basis of retesting after 2 months or on their clinical response to thyroid replacement therapy over at least 2 months. The enzyme immunoassay evaluated in this paper is considered to be of clinical value and offers many advantages compared with radioimmunoassays.

Haemopoietic progenitor cell differentiation: flow cytometric assessment in bone marrow and thymus.

We have recently shown that expression of any of the lineage-associated molecules CD2, CD7, CD10, CD19 or CD33 does not ensure lineage-commitment of CD34+ progenitor cells. Further, normal progenitor cells and leukaemic blast cells have been shown to coexpress molecules associated with more than one haemopoietic lineage. Five-dimensional flow cytometric analysis of normal bone marrow cells was exploited to investigate the hypothesis of a developmental stage in haemopoiesis comprising CD34+ cells coexpressing CD2, CD5, CD7, CD10, CD19 and CD33 or any combination of these molecules. We report on a subpopulation of CD34+ bone marrow cells constituting < 5% of the CD34+ cells and characterized by extensive coexpression of several molecules associated with the B lymphoid, T lymphoid and myeloid lineages. There is every probability that some cells display the CD34+ CD2+ CD5+ CD7+ CD10+ CD19+ CD33+ phenotype. Studies on postnatal thymocytes suggest that this may be the phenotype or one of a few phenotypes of a candidate thymus-seeding progenitor cell population. Finally, our findings that CD34+ as well as CD34+ CD5+ thymocytes can be driven into non-T-lymphoid differentiation by cytokines, support the notion that the thymus is seeded by uncommitted progenitors.

Frequency of hyperprolactinaemia due to large molecular weight prolactin (150-170 kD PRL).

Of 605 hyperprolactinaemic sera (prolactin > 1000 mU l-1 determined with PRL DELFIA, Wallac) in the routine diagnostic (PRL was measured in 10,737 sera) 26% had an increased amount of PRL with molecular weight (MW) = 150-170 kD (150-170 kD PRL or bigbig PRL). In a series of serum samples from 660 healthy subjects, only one female with hyperprolactinaemia due to increased 150-170 kD PRL was found. The 150-170 kD PRL constituted less than 1% of the total PRL found in 11 patients with prolactinoma (macroprolactinoma, PRL 8800-500,000 mU l-1). When determined with five different commercially available immunometric assays, the PRL values in the sera with large amounts of 150-170 kD were increased in all sera in four of five assays, although they varied widely. The clinical implications of hyperprolactinaemia due to increased 150-170 kD PRL are still uncertain.

Anal endosonography and physiology in adolescents with corrected low anorectal anomalies.

Sixteen patients aged 12 to 16 years (mean, 14.9) with corrected low anorectal anomalies, and eight age-matched controls were studied. Eight patients were totally continent, six had staining, and two had fecal soiling. Half the patients had trouble with constipation. The grade of incontinence was related to significantly reduced resting and squeeze pressure in the anal canal. Girls had significantly worse results than boys. The anal sphincter muscle complex was visualized by anal endosonography, and images of the external anal sphincter corresponded to the results of the surface electromyography. In addition, anal endosonography provided a detailed picture of all perianal structures including the internal anal sphincter. Anal endosonography supplements other imaging techniques for assessing the perianal structures in patients who have an accessible anal canal.

c-kit ligand combined with GM-CSF and/or IL-3 can expand CD34+ hematopoietic progenitor subsets for several weeks in vitro.

It might be possible to facilitate engraftment after transplantation of purified hematopoietic progenitor cells if the cells are stimulated ex vivo prior to transplantation. The aim of this study was to analyze the potential of c-kit ligand (CKL) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin-3 (IL-3) to induce proliferation and differentiation of human bone marrow CD34+ cells in vitro. Particular attention was paid to the ability to expand populations that could maintain progenitor characteristics, i.e. CD34 expression and generation of colony forming cells (CFC), for a considerable period of time. Purified CD34+ cells were cultured in liquid medium for 42 days interrupted by immunophenotyping and CFC assays. In the presence of CKL combined with GM-CSF and/or IL-3, the total number of cells expressing CD34 increased significantly for several weeks after an initial decline. Further, CFC were continually recovered in these cultures. Based on the kinetics and the flow cytometry analysis, the expanding populations that continued to express CD34 probably originated from noncommitted, immature CD34+ cell subsets. CKL combined with GM-CSF and/or IL-3 also induced strong cell proliferation. The majority of the proliferating cells lost CD34 expression and acquired a series of mature myeloid cell surface markers associated with the monocytic, granulocytic and megakaryocytic lineages. These cells probably originated from committed CD34+ cell subsets. We conclude that CKL combined with GM-CSF and/or IL-3 can stimulate noncommitted, immature as well as committed CD34+ cell populations to expand and to differentiate. This property might be useful in a short-term ex vivo pretransplant stimulation of CD34+ cells in an attempt to facilitate rapid and stable engraftment after stem cell transplantation.

Metallothionein: a protein conferring resistance in vitro to tumor necrosis factor.

The role of metallothionein (MT) in the cytotoxicity of tumor necrosis factor (TNF) was investigated in vitro. A human epithelial cell line (HE100) and a mouse fibroblast line (CI 1D100) had previously been cultured to become resistant to 100 microns CdCl2 and were cultured routinely in cadmium-containing medium. The MT content of these cells and the nonresistant parent cell lines (HE and CI 1D) was determined both qualitatively and quantitatively by immunochemical techniques. Immunofluorescence microscopy revealed the cadmium-resistant cell lines to be intensely rich in MT in both the nuclear and cytoplasmic compartments. This finding was confirmed by immuno-electron microscopy which also showed the labeling to be freely distributed and not membrane-bound. In comparison, a very weak labeling of the parent cell lines was observed. MT concentration, as determined by enzyme-linked immunosorbant assay, was found to be 4.05 +/- 1.13% and 3.91 +/- 0.7% of the total protein for HE100 and CI 1D100 cells, respectively. We were unable to detect MT in the parent cell lines by this technique. Dose-survival curves obtained after 3 days treatment of the cells with TNF (0.125-500 ng/ml) revealed that the MT-rich substrains were significantly resistant compared to the parent strains (P < 0.001; t tests). In growth rate studies, where cells were exposed to TNF over a dose range of 0.25-250 ng/ml for 6 days, the resistance of the MT-rich cell lines was confirmed (P < 0.002). These data indicate that MT confers resistance to the cytotoxic effects of TNF in vitro and that sensitivity to TNF may be related to the MT content of the cell.

Electrodermal and microcirculatory activity in patients with fibromyalgia during baseline, acoustic stimulation and cold pressor tests.

The peripheral sympathetic activity was studied in 27 patients with fibromyalgia and 29 healthy controls through simultaneous measurements of electrodermal variables and blood flow at palmar skin sites during baseline, acoustic stimulation, and cold pressor tests. Compared to the controls, the patient group showed a significantly larger overall increase in the skin electrical conductance and less vasoconstriction during acoustic stimulation and cold pressor tests. These findings imply an increased activity of cholinergic and decreased activity of adrenergic components of the peripheral sympathetic nervous system in patients with fibromyalgia.

Long-term toxicity of preoperative 4'-epidoxorubicin (Epi-adriamycin) in partially hepatectomized rats.

4'-Epidoxorubicin (Epi-A) administered immediately prior to liver resection has been suggested as treatment for patients with primary liver carcinoma. Long-term toxicity was studied in rats given a single dose of Epi-A intravenously immediately prior to a standard partial hepatectomy (PH). After 52 weeks only 9% of the rats given 5 mg/kg + PH were alive, 79% of the rats given 2 mg/kg + PH and 92% of the PH control survived. The weight gain of the rats given 5 mg/kg + PH was only 17% of that of PH controls. Signs of congestive heart failure were observed in some rats while in others moderate kidney lesions. No histopathological lesions were detected by light microscopy in heart, liver, spleen and bone marrow. For the rats given 2 mg/kg + PH body weight gain, microscopic observations and blood chemistry data (total protein, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin, creatinine and urea) were comparable to the PH controls. No significant differences in survival were registered between partially hepatectomized and sham-operated rats. The results indicate that Epi-A may be given preoperatively to liver resection without inducing long-term effects on vital organs.

Altered sympathetic nervous system response in patients with fibromyalgia (fibrositis syndrome).

Twenty-seven female patients with fibromyalgia and 29 female healthy controls underwent an auditive stimulation test and a left hand cold pressor test at 10 and 4 degrees C. The microcirculatory changes observed, indicate that, as a response to 80 dB, 1000 Hz, 2 seconds sounds and cooling with associated pain, the vasoconstrictory responses are less in patients with fibromyalgia than in normal controls. This could indicate altered sympathetic nervous activity in patients with fibromyalgia and that the cutaneous manifestations previously interpreted as Raynaud's phenomenon should be reconsidered.

Failed ileoanal anastomosis: correlations between clinical function and anal canal neurophysiologic and histologic examinations.

Ten patients with an ileoanal anastomosis had conversion to permanent ileostomy 13 (range, 6-29) months after the primary procedure. Causes for reoperation were incontinence in seven patients, unacceptable stool frequency without incontinence in two patients, and atypia in the mucosal remnant with perfect continence in one patient. Stool frequency, continence function, anal canal resting pressure, external anal sphincter (EAS) EMG/pressure relationship (in terms of slope, m), EAS fiber density (FD), and pressure in the distal ileum were registered, and the mucosa and the anal sphincter muscles were examined histologically. There were significant correlations between continence function and EAS changes in terms of both neurophysiologic tests (m and FD) and the histologic picture. The abnormalities in six incontinent patients were consistent with denervation of the EAS. The main reason for fecal leakage in one patient was the high amplitude of pressure waves in the distal ileum. Preservation of mucosal epithelium proximal to the dentate line per se did not seem essential to maintain continence.

Attention deficit disorders: a study of peptide-containing urinary complexes.

In several behavioral disorders, we have observed that abnormal amounts of peptides and protein-associated peptide complexes are excreted in the urine. The gel filtration patterns of these excreted substances have some specificity for the different disorders. The urinary excretion of peptide-containing complexes was studied in 91 boys and 13 girls (mean age 9.4 years, range 1-23) with the clinical diagnosis of attention deficit disorder (ADD), with or without hyperactivity. The gel filtration of urine precipitate showed patterns in all patients that were different from those seen in 36 normal controls. Sixty-four patients had increased benzoic acid-glycoprotein-peptide complexes in the late peaks. The symptoms of all these patients fit the criteria for diagnosis of attention deficit disorder with hyperactivity (ADDH). Thirty-five patients showed reduced amounts of uric acid complexes in the late peaks. Clinically, this group, with the exception of three patients, fit the criteria for diagnosis of attention deficit disorder without hyperactivity. Five patients showed reduced amounts of all urinary complexes; four of these were hyperactive. Moderate exercise in control children did not change the urinary pattern. One urinary peptide fraction from hyperactive patients, purified to homogeneity, increased the uptake of 14C[5-HT] in platelets. Strict clinical, neuropsychological, and psychophysiological selection of the patients reduced the heterogeneity of the patterns. Although more studies are needed, the findings seem promising for the possibility of developing biochemical tests that may be helpful diagnostically.