Adherence to guideline recommendations for Barrett's esophagus (BE) surveillance endoscopies: Effects of dedicated BE endoscopy lists.

Background and study aims For non-dysplastic Barrett's Esophagus (BE) patients, guidelines recommend endoscopic surveillance every 3 to 5 years with four-quadrant random biopsies every 2 cm of BE length. Adherence to these guidelines is low in clinical practice. Pooling BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists could possibly enhance guideline adherence, detection of visible lesions, and dysplasia detection rates (DDRs). Patients and methods Data were used from the ACID-study (Netherlands Trial Registry NL8214), a prospective trial of BE surveillance in the Netherlands. BE patients with known or previously treated dysplasia were excluded. Guideline adherence, detection of visible lesions, and DDRs were compared for patients on dedicated and general endoscopy lists. Results A total of 1,244 patients were included, 318 on dedicated lists and 926 on general lists. Endoscopies on dedicated lists showed significantly higher adherence to the random biopsy protocol (85% vs. 66%, P <0.01) and recommended surveillance intervals (60% vs. 47%, P <0.01) compared to general lists. Detection of visible lesions (8.8% vs. 8.1%, P =0.79) and DDRs were not significantly different (6.9% and 6.6%, P =0.94). None (0.0%) of the patients scheduled on dedicated lists and 10 (1.1%) on general lists were diagnosed with esophageal adenocarcinoma ( P =0.07). In multivariable analysis, dedicated lists were significantly associated with biopsy protocol adherence and adherence to surveillance interval recommendations with odds ratios of 4.45 (95% confidence interval [CI] 2.07-9.57) and 1.64 (95% CI 1.03-2.61), respectively. Conclusions Dedicated endoscopy lists are associated with better adherence to the random biopsy protocol and surveillance interval recommendations.

[Severe malnutrition after gastric: the importance of lifelong follow-up]. / Ernstige malnutritie na gastric bypass.

Two cases are described of patients who present with severe malnutrition more than five years after undergoing a Roux-en-Y gastric bypass and who have deficiencies of both micronutrients (vitamins and minerals) and macronutrients (proteins). This problem appears to be caused by both iatrogenic malabsorption after gastric bypass as well as dysphagia due to a local anastomotic complication (stenosis and marginal ulcer). Although both the severity of the deficiencies and the timing are exceptional, we want to emphasize the importance of lifelong supplement use and follow-up after bariatric surgery. Given the important role of general practitioners in this, we argue for implementation of this topic in national guidelines to improve the quality of follow-up.

Tachyduodenia in mitochondrial neurogastrointestinal encephalomyopathy.

In a 38-year-old male patient diagnosed with mitochondrial neurogastrointestinal encephalomyopathy an abnormally high duodenal contraction frequency of 20 per minute was found to be present. It is speculated that this tachyduodenia is caused by a metabolic effect on Cajal cells.

Effect of proximal gastric volume on hiatal hernia.

BACKGROUND: Spatial separation of the diaphragm and the lower esophageal sphincter (LES) occurs frequently and intermittently in patients with a sliding hiatus hernia and favors gastro-esophageal reflux. This can be studied with high-resolution manometry. Although fundic accommodation is associated with a lower basal LES pressure, its effect on esophagogastric junction configuration and hiatal hernia is unknown. Therefore, the aim of this study was to investigate the relationship between proximal gastric volume, the presence of a hiatal hernia profile and acid reflux. METHODS: Twenty gastro-esophageal reflux disease (GERD) patients were studied and compared to 20 healthy controls. High-resolution manometry and pH recording were performed for 1 h before and 2 h following meal ingestion (500 mL per 300 kcal). Volume of the proximal stomach was assessed with three-dimensional ultrasonography before and every 15 min after meal ingestion. KEY RESULTS: During fasting, the hernia profile [2 separate high-pressure zones (HPZs) at manometry] was present for 31.9 +/- 4.9 min h(-1) (53.2%) in GERD patients, and 8.7 +/- 3.3 min h(-1) (14.5%) in controls (P < 0.001). In GERD patients, the presence of hernia profile decreased during the first postprandial hour to 15.9 +/- 4.2 min h(-1), 26.5%, P < 0.01 whilst this phenomenon was not observed in controls. The rate of transition between the two profiles was 5.7 +/- 1.1 per hour in GERD patients and 2.5 +/- 1.0 per hour in controls (P < 0.001). The pre and postprandial acid reflux rate in GERD patients during the hernia profile (6.4 +/- 1.1 per hour and 18.4 +/- 4.3 per hour respectively) was significantly higher than during reduced hernia (2.1 +/- 0.6 per hour; P < 0.05 and 3.8 +/- 0.9 per hour; P < 0.05). A similar difference was found in controls. Furthermore, an inverse correlation was found between fundic volume and the time the hernia profile was present (r = -0.45; P < 0.05) in GERD patients, but not in controls. CONCLUSIONS & INFERENCES: (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra-thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion.

Randomized clinical trial of standard laparoscopic versus robot-assisted laparoscopic Nissen fundoplication for gastro-oesophageal reflux disease.

BACKGROUND: Robotic systems for minimally invasive surgery may be of added value during extensive dissection and suturing in confined spaces, such as laparoscopic Nissen fundoplication (LNF). The purpose of this trial was to compare standard LNF with robot-assisted Nissen fundoplication (RNF). METHODS: Between 2003 and 2005, 50 patients with confirmed refractory gastro-oesophageal reflux disease were assigned to LNF (25) or RNF (25). Patients who had undergone previous antireflux surgery were excluded. Independent assessment of dysphagia, regurgitation, heartburn and general well-being was performed before and 6 months after surgery using questionnaires. Objective outcome was studied 6 months after surgery by oesophageal manometry, 24-h pH monitoring, barium oesophagram series and upper endoscopy. RESULTS: Operating time, blood loss, postoperative pain scores, hospital stay and complication rates did not differ significantly between the two groups. Reoperation rates were the same (one incisional hernia after LNF and one patient with repeat Nissen after RNF because of persistent dysphagia). Postoperative self-rated change in reflux symptoms and quality of life improved equally in both groups. The reduction in oesophageal acid exposure, increase in lower oesophageal sphincter tone and mucosal healing were comparable in both groups at follow-up. CONCLUSION: RNF yielded similar subjective and objective results to LNF in this study. Therefore no additive value of robotic systems for this procedure was detected up to 6 months after surgery.

Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease.

This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour ambulatory manometry and pH recording. In the 3-hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 +/- 23 s and 41 +/- 5 s, respectively, P < 0.001). In the 24-hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.

Impaired bolus transit across the esophagogastric junction in postfundoplication dysphagia.

OBJECTIVES: This study assessed the effect of fundoplication on liquid and solid bolus transit across the esophagogastric junction (EGJ) in relation to EGJ dynamics and dysphagia. METHODS: Twelve patients with gastro-esophageal reflux disease (GERD) were studied before and after fundoplication. Concurrent high-resolution EGJ manometry and fluoroscopy were performed whilst swallowing liquid barium and a solid bolus. The EGJ transit time, EGJ opening duration, transit efficacy, and EGJ relaxation were measured. During the test symptoms of dysphagia were scored using a visual analog scale. RESULTS: The minimal opening aperture at fluoroscopy was located at the manometric EGJ in all subjects. Fundoplication markedly reduced the EGJ opening diameter from 1.0 +/- 0.1 to 0.6 +/- 0.1 cm (p < 0.01) and rendered deglutative EGJ relaxation incomplete. After fundoplication, a higher intrabolus pressure was found (p < 0.05) associated with a reduced axial bolus length (p < 0.001). EGJ transit time increased from 6.9 +/- 0.9 to 9.8 +/- 1.0 s for liquids (p < 0.01) and from 2.8 +/- 0.5 to 5.8 +/- 0.8 s (p < 0.01) for solids after fundoplication. No relation between EGJ transit and dysphagia scores was observed before fundoplication. In contrast, EGJ transit time significantly correlated with dysphagia scores both during liquid (r = 0.84; p < 0.01) and solid (r = 0.69; p < 0.05) bolus transit following fundoplication. CONCLUSIONS: Fundoplication patients exhibit a restricted hiatal opening and an incomplete deglutative EGJ relaxation. To facilitate EGJ transit despite these altered EGJ dynamics a higher intrabolus pressure is created by augmented bolus compression. Fundoplication increases EGJ transit time, the degree of which is associated with postoperative dysphagia.

The diagnosis of preschool bipolar disorder presenting with mania: open pharmacological treatment.

BACKGROUND: Diagnosis of bipolar disorder (BPD) in preschool children is controversial, although preliminary data suggest that children with BPD may present with classic manic symptoms in a more chronic, rapid cycling presentation. While children with BPD are extremely dysfunctional, presenting symptoms and symptom expression remains to be further defined. Clarification of the presentation of BPD in children could result in better treatment. METHODS: Thirty-one patients, ages 2-5 years, were identified by chart review of all children treated at our pediatric bipolar clinic. All available historical, symptom, and treatment information was collected and summarized. RESULTS: Patients were approximately 2:1 male: female, predominantly Caucasian, with an average age of symptom onset of 3 years. Most frequent presenting symptoms (100%) included irritability, increased energy, and aggression. Prominent symptoms (>80%) included euphoria, grandiosity, decreased need for sleep, pressured speech, and distractibility. Eighty percent of patients had concurrent Attention-Deficit Hyperactivity Disorder (ADHD). Twenty-one of the 31 patients reported prior treatment attempts with either a stimulant or antidepressant without the protective benefit of a mood stabilizer, and of these, 13 (62%) reported a worsening of mood symptoms during that treatment period. Twenty-six of 31 were initially treated in our clinic openly with a mood stabilizer, primarily valproic acid, with a significant decrease in manic symptoms (p=0.03) following initial treatment. Long-term treatment demonstrated continued improvements from baseline (p=0.01). LIMITATIONS: The retrospective design of this study limits the conclusions that can be drawn. Due to the lack of a formal protocol, treatment was open and based on clinical judgment on an individual case basis. CONCLUSIONS: The symptom expression in these patients allowed for diagnosis according to DSM-IV criteria. Treatment with mood stabilizers was clinically effective, with corresponding significant developmental benefits.

Relationship between partial gastric volumes and dyspeptic symptoms in fundoplication patients: a 3D ultrasonographic study.

OBJECTIVES: Impaired gastric accommodation may induce dyspeptic symptoms in postfundoplication patients. Our aim was to assess the effect of a meal on total and partial gastric volumes in relation to dyspeptic symptoms in both dyspeptic and nondyspeptic fundoplication patients using three-dimensional (3D) ultrasonography. METHODS: Eighteen postfundoplication patients of whom eight with and ten without dyspeptic symptoms and eighteen controls were studied. Three-dimensional ultrasonographic images of the stomach were acquired and symptoms were scored while fasting and at 5, 15, 30, 45, and 60 min after ingesting of a 500-ml liquid meal. From the 3D ultrasonographic images of the stomach the total, proximal, and distal gastric volumes were computed. RESULTS: Dyspeptic and nondyspeptic fundoplication patients exhibited similar total gastric volumes at 5 min postprandially compared to controls, whereas smaller total gastric volumes were observed from 15 to 60 min postprandially (p = 0.007 and p < 0.001, respectively). Postprandial proximal/total gastric volume ratios were markedly reduced in both dyspeptic (0.39 +/- 0.016; p < 0.05) and nondyspeptic (0.38 +/- 0.016; p < 0.01) fundoplication patients compared to controls (0.47 +/- 0.008). In contrast, distal/total gastric volume ratios were larger in dyspeptic fundoplication patients (0.14 +/- 0.008) compared to both nondyspeptic fundoplication patients (0.11 +/- 0.007); p < 0.05) and controls (0.07 +/- 0.003); p < 0.001). Dyspeptic fundoplication patients had a higher postprandial score for fullness, nausea, and pain than nondyspeptic patients (p < 0.05) and controls (p < 0.05). Meal-induced distal gastric volume increase correlated significantly with the increase in fullness (r = 0.68; p < 0.01). CONCLUSIONS: After a liquid meal, fundoplication patients exhibit a larger volume of the distal stomach compared with controls. Distal stomach volume was more pronounced in dyspeptic fundoplication patients and related with the increase in postprandial fullness sensations.

Long-term effect of fundoplication on motility of the oesophagus and oesophagogastric junction.

BACKGROUND: This study assessed the long-term effect of Nissen fundoplication on oesophageal and oesophagogastric junction (OGJ) motility. METHODS: Symptoms were scored and oesophageal manometry performed in 34 consecutive patients with chronic gastro-oesophageal reflux disease, before, 3 months after and 2 years after surgery. RESULTS: Distal peristaltic amplitude increased from a median of 57 (95 per cent confidence interval (c.i.) 18 to 107) mmHg to 86 (95 per cent c.i. 54 to 208) mmHg (P < 0.001) at 3 months and 92 (45 to 210) mmHg (P < 0.001) at 2 years. In four patients the amplitude increased to more than 180 mmHg and three of these patients reported odynophagia. After surgery, a linear relationship was observed between the peristaltic amplitude and nadir OGJ relaxation pressure at 3 months (r(s) = 0.68, P < 0.001) and 2 years (r(s) = 0.64, P < 0.001). A significant correlation was also found between amplitude and both basal OGJ pressure and intrabolus pressure at 3 months (r(s) = 0.58, P < 0.001 and r(s) = 0.63, P < 0.001 respectively) and 2 years (r(s) = 0.71, P < 0.001 and r(s) = 0.49, P = 0.024). There was a relationship between peristaltic amplitude and the odynophagia score at 2 years (r(s) = 0.60, P = 0.017). CONCLUSION: Within 3 months of fundoplication the amplitude of oesophageal peristalsis increased substantially, leading to a nutcracker oesophagus and odynophagia in a subgroup of patients. These phenomena did not appear to progress with time.

Reduced tLESR elicitation in response to gastric distension in fundoplication patients.

Transient lower esophageal sphincter relaxations (tLESRs) are vagally mediated in response to gastric cardiac distension. Nine volunteers, eight gastroesophageal reflux disease (GERD) patients, and eight fundoplication patients were studied. Manometry with an assembly that included a barostat bag was done for 1 h with and 1 h without barostat distension to 8 mmHg. Recordings were scored for tLESRs and barostat bag volume. Fundoplication patients had fewer tLESRs (0.4 +/- 0.3/h) than either normal subjects (2.4 +/- 0.5/h) or GERD patients (2.0 +/- 0.3/h). The tLESRs rate increased significantly in normal subjects (5.8 +/- 0.9/h) and GERD patients (5.4 +/- 0.8/h) during distension but not in the fundoplication group. All groups exhibited similar gastric accommodation (change in volume/change in pressure) in response to distension. Fundoplication patients exhibit a lower tLESR rate at rest and a marked attenuation of the response to gastric distension compared with either controls or GERD patients. Gastric accommodation was not impaired with fundoplication. This suggests that the receptive field for triggering tLESRs is contained within a wider field for elicitation of gastric receptive relaxation and that only the first is affected by fundoplication.

Elicitation of transient lower oesophageal sphincter relaxations in response to gastric distension and meal ingestion.

The aim of this study was to compare the effect of graded gastric barostat distension and meal-induced fundic relaxation on the elicitation of transient lower oesophageal sphincter relaxation (TLOSR). In 15 healthy subjects, stepwise fundic distension and oesophageal manometry were performed simultaneously. Next, the effect of meal ingestion on proximal stomach volume and lower oesophageal sphincter function was studied. During stepwise barostat distension of the proximal stomach, a significant linear correlation between intragastric pressure (r = 0.91; P < 0.01) and the TLOSR rate during inflation and subsequent deflation (r = 0.96; P < 0.01) was found. A similar relationship was found for volume. In addition, after meal ingestion, the TLOSR rate increased significantly from 1.40 +/- 3 to 5.4 +/- 1.5 h-1 (P < 0.01) and 5.2 +/- 1.7 h-1 (P < 0.01), respectively, during the first and second 30-min postprandially. However, at similar calculated intragastric volumes, barostat distension led to a significantly higher TLOSR rate than the meal. Similarly, distension-induced increase in gastric wall tension, estimated from the measured bag pressure and volume using Laplace's law, was associated with significantly higher TLOSR rates (P < 0.01). In conclusion, the rate of TLOSRs in healthy volunteers is directly related to the degree of proximal gastric distension and pressure-controlled barostat distension is a more potent trigger of TLOSRs than a meal. The latter finding suggests that tension receptor activation is an important stimulus for TLOSRs.

Inhibition of vascular NADH/NADPH oxidase activity by thiol reagents: lack of correlation with cellular glutathione redox status.

Vascular NAD(P)H oxidase activity contributes to oxidative stress. Thiol oxidants inhibit leukocyte NADPH oxidase. To assess the role of reactive thiols on vascular oxidase, rabbit iliac/carotid artery homogenates were incubated with distinct thiol reagents. NAD(P)H-driven enzyme activity, assessed by lucigenin (5 or 250 microM) luminescence, was nearly completely (> 97%) inhibited by the oxidant diamide (1mM) or the alkylator p-chloromercuryphenylsulfonate (pCMPS, 0.5mM). Analogous inhibition was also shown with EPR spectroscopy using DMPO as a spin trap. The oxidant dithionitrobenzoic acid (0.5mM) inhibited NADPH-driven signals by 92% but had no effect on NADH-driven signals. In contrast, the vicinal dithiol ligand phenylarsine oxide (PAO, 1 microM) induced minor nonsignificant inhibition of NADPH-driven activity, but significant stimulation of NADH-triggered signals. The alkylator N-ethyl maleimide (NEM, 0.5mM) or glutathione disulfide (GSSG, 3mM) had no effect with each substrate. Coincubation of N-acetylcysteine (NAC, 3mM) with diamide or pCMPS reversed their inhibitory effects by 30-60%, whereas NAC alone inhibited the oxidase by 52%. Incubation of intact arterial rings with the above reagents disclosed similar results, except that PAO became inhibitor and NAC stimulator of NADH-driven signals. Notably, the cell-impermeant reagent pCMPS was also inhibitory in whole rings, suggesting that reactive thiol(s) affecting oxidase activity are highly accessible. Since lack of oxidase inhibition by NEM or GSSG occurred despite significant cellular glutathione depletion, change in intracellular redox status is not sufficient to account for oxidase inhibition. Moreover, the observed differences between NADPH and NADH-driven oxidase activity point to complex or multiple enzyme forms.

Elevated plasma lipid peroxides at the onset of nonaffective psychosis.

BACKGROUND: Impaired antioxidant defense and increased lipid peroxidation has been reported in chronic schizophrenic patients. Recently, we have reported an impaired antioxidant defense in never medicated first-episode schizophrenic and schizophreniform patients. We report now a concomitant increase in plasma lipid peroxides. METHODS: The plasma lipid peroxides [thiobarbituric acid reactive substances (TBARS)] were analyzed by chemical and high performance liquid chromatography procedures in 26 patients admitted for a first episode of schizophrenic (N = 17) or schizophreniform psychosis (N = 9) and 16 normal control subjects. The patients had a duration of 4.5 days (SD 2.8) of psychosis at the time of the study. RESULTS: Plasma TBARS levels were significantly higher in the patients than in normal controls (P < .002). TBARS levels were above the normal range in 16 of the 26 patients. Higher TBARS levels were associated with a greater severity of negative symptoms and lower red blood cell activity of the glutathione peroxidase. CONCLUSIONS: The findings indicate ongoing oxidative injury at the very onset of psychosis. If valid, this would indicate the need for adjunctive antioxidant treatment from the beginning of the course of nonaffective psychoses. This might prevent a deteriorating course and development of the deficit syndrome.

Oxidative injury and potential use of antioxidants in schizophrenia.

There is increasing evidence that oxidative injury contributes to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and CSF, and altered levels of both enzymatic and non-enzymatic antioxidants in chronic and drug-naive first-episode schizophrenic patients. The increased plasma lipid peroxidation is also supported by concomitant lower levels of esterified polyunsaturated essential fatty acids of red blood cell plasma membrane phospholipids. Because membrane phospholipids play a critical role in neuronal signal transduction, oxidative damage of these lipids may contribute to the proposed altered neurotransmitter receptor-mediated signal transduction and thereby alter information processing in schizophrenia. Adjunctive treatment with antioxidants (e.g. vitamins E and C, beta-carotene and quinones) at the initial stages of illness may prevent further oxidative injury and thereby ameliorate and prevent further possible deterioration of associated neurological and behavioral deficits in schizophrenia.

Utilization of precursor essential fatty acids in culture by skin fibroblasts from schizophrenic patients and normal controls.

Based on the lower levels of long-chain polyunsaturated analogs of essential fatty acids (EPUFAs) in plasma membrane phospholipids of red blood cells, brain and cultured skin fibroblasts from schizophrenic patients, a defective utilization (uptake, conversion to EPUFAs and incorporation into membrane phospholipids) of precursor EFAs has been suggested. Utilization of radiolabeled linoleic (LA, 18:2(n-6)) and alpha-linolenic (ALA, 18:3(n-3)) acids was studied in cultured skin fibroblasts from patients with established schizophrenia and at the first episode of psychosis, and normal controls. Uptake and incorporation of both the EFAs were similar in fibroblasts from both groups of patients studied compared with normal controls. However, although the utilization of LA into arachidonic acid (AA, 20:4n-6) was similar in patients and controls, the utilization of eicosapentaenoic acid (EPA, 20:5(n-3)) into docosahexaenoic acid (DHA, 22:6(n-3)) was significantly lower in first-episode psychotic patients (patients, 96.33 +/- 27.16 versus normals, 161.66 +/- 26.33 nmoles per mg total protein; P = < 0.001). This data indicates that the level of delta 6- as well as delta 5-desaturase may be normal. However, the levels of delta 4-desaturase may be lower in fibroblasts from schizophrenic patients even at the first episode of psychosis.

Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from schizophrenic patients: comparison with bipolar patients and normal subjects.

Recent studies have found lower red cell plasma membrane contents and composition of the long chain polyunsaturated essential fatty acid derivatives, particularly arachidonic acid and docosahexaenoic acid, in a subgroup of chronic schizophrenic patients. These fatty acids are particularly enriched in the brain. Red blood cell levels of fatty acids are influenced by diet, medications, and other factors. Cell plasma membrane compositions of arachidonic and docosahexaenoic acids were therefore examined in cultured skin fibroblasts from 12 schizophrenic patients, 8 of whom were drug-naive and in a first episode of psychosis, 6 bipolar patients, and 8 normal control subjects. Docosahexaenoic acid as well as total n-3 essential fatty acid contents were significantly lower in cell lines from schizophrenic patients than in cell lines from bipolar patients and normal subjects, with no difference between the latter two groups. Arachidonic acid levels did not differ across the groups. The essential fatty acid profile observed is consistent with deficient delta-4 desaturase activity in schizophrenic patients.

Impaired antioxidant defense at the onset of psychosis.

Previous studies found peripheral activities of antioxidant enzymes to be abnormal in schizophrenic patients. It is not understood whether this is integral to the disease process or a result of long-term treatment with neuroleptics. Red blood cell activities of three antioxidant enzymes--superoxide dismutase, glutathione peroxidase, and catalase--were therefore examined in 14 drug-naive, first episode patients with a diagnosis of schizophrenia or schizophreniform disorder and 10 normal subjects. The patients had an average duration of psychosis of 4.46 days (SD 2.5). Superoxide dismutase activity was significantly lower in patients than in normal controls, with no difference between the groups in activities of the other two enzymes. Lower superoxide dismutase activity was associated with deterioration of school functioning from childhood to early adolescence and a history of poorer school functioning during early adolescence. These findings indicate a compromised antioxidant defense at the onset of psychosis, and suggest that oxidative injury might contribute to adverse developmental events in the pathogenic cascade of schizophrenia.