The natural history of perforated foregut ulcers after repair by omental patching or primary closure.

BACKGROUND: The treatment of perforated foregut ulcers by omental patching (OP) or primary closure has mostly replaced vagotomy and pyloroplasty/antrectomy (VPA). We sought to determine the natural history and recurrence rate of ulceration in patients treated by omental patching or primary closure. STUDY DESIGN: An 11-year retrospective study. RESULTS: From 2004 through 2015, 94 patients had perforated foregut ulcers, 53 gastric, and 41 duodenal. 77 (82%) were treated by OP alone (study group) and 17 (18%) were treated with VPA (comparison group). All OP patients were discharged on PPIs, but only 86% took the drugs for a median of 22 months (1-192, SD 40). Endoscopy in the OP group showed recurrent ulcers in nine (12% recurrence rate) and gastritis in three (4%) This group also had three later recurrent perforations. Another recurrent ulcer hemorrhaged causing death (3% late mortality). Two other patients required non-emergent re-do ulcer operations for recurrent disease/symptoms (surgical re-intervention rate 4%). Total length of follow-up was median 44 months (1-192, SD 40) and was complete in 82 (87%). 18 (23%) patients in the OP group developed recurrent abdominal pain attributed to ulcer disease during follow-up, compared to 2 (12%) in the VPA group (p = 0.15). No patient in the VPA group had an endoscopic recurrence or re-intervention. CONCLUSION: Omental patching does not correct the underlying disease process which causes foregut perforation, and has a 12% endoscopically proven recurrent ulceration rate and a 23% incidence of recurrent symptoms within 44 months. Patients tend to stop taking PPIs after 22 months at which time their risk increases.

The role of computed tomography in determining delayed intervention for gunshot wounds through the liver.

INTRODUCTION: Gunshot wounds through the liver are highly lethal and are prone to delayed morbidity due to late complications. METHODS: A retrospective study was performed to determine the incidence, morbidity, and need for late interventions in patients shot through the liver, and the role of post-injury CT in making those determinations. RESULTS: 83 patients were shot through the liver. Injury grades were: Grade V-12 (14 %), Grade IV-41 (49 %), Grade III-12 (14 %), Grade II-8 (10 %), Grade I-1 (1 %), and nine were ungraded. Ten (12 %) died in the ED, three (4 %) died in the OR, and two (2 %) died postoperatively. Of the 68 survivors, 52 (76 %) had follow-up CT scans performed a median of 7 days (95 % CI 2-13 days) after injury. Seventeen (33 %) had 25 complications related to the bullet tract: 12 (48 %) abscesses, 6 (24 %) infected hematomas, 3 (12 %) bilomas, 3 (12 %) unclassified fluid collections, and 1 (4 %) hepatic necrosis. Treatment included CT-guided drainage in 15 (60 %), ultrasound-guided drainage in 3 (12 %), surgical drainage and debridement in 2 (8 %), and observation in 5 (20 %). Overall morbidity rate including hepatic and non-hepatic complications was 74 % (50/68). Patients having their CT scan-determined intervention (for all complications) within 7 days of injury (n = 24), compared to those having their CT scan-determined intervention on day 8 or later (n = 28), had a significantly decreased rate of overall complications and morbidity (p = 0.03). This difference was due to early detection and intervention for abscesses, anastomotic breakdown, and missed injuries. Those having a CT scan within 7 days of injury also had a significantly reduced length of stay compared to those scanned on day 8 or later (median 14 days, 95 % CI 4-24 days versus 18 days, 95 % CI 6-30 days, p = 0.05). CONCLUSIONS: Gunshot wounds to the liver have a high morbidity and mortality rate. Survivors should have a follow-up CT scan performed within 7 days to allow detection and intervention for complications, as this dramatically decreases the overall morbidity rate and length of stay.

Clinical Findings and Genetic Screening for Copy Number Variation Mutations in a Cohort of South African Patients with Parkinson's Disease

BACKGROUND:Parkinson's disease (PD); with a prevalence of up to 4% in Western countries; appears to be less common in Africa; possibly in part because of genetic factors. African studies investigating the genetic causation of PD are limited. OBJECTIVE:To describe the clinical and genetic findings in a group of black South African patients with PD.METHODS:All black African patients with PD from a tertiary hospital neurology clinic were examined. Symptoms were scored according to the Unified Parkinson's Disease Rating Scale (UPDRS); and patients were classified according to motor features. Genomic DNA was extracted and multiplex ligation-dependent probe amplification was used for detection of copy number variation (CNV) mutations in the known PD-causing genes.RESULTS:Sixteen patients were identified (ages 56 - 82 years). Three had a family history of PD. Classification into motor subtypes showed 44% mixed; 31% akinetic-rigid; and 25% tremor-dominant subtypes. UPDRS scores ranged from 7 to 88; with dementia in 20%. No patient had G2019S LRRK2 and A30P SNCA mutations; and all except one had no CNV mutations in the known PD-causing genes. A female patient (age of onset 50 years; no family history) had a parkin gene heterozygous deletion of exon 4. She had hyperreflexia; bilateral Hoffmann's reflexes; normal plantar responses and no dystonia.CONCLUSION:This group of black African patients showed similar characteristics to patients in Western studies; possibly with a higher proportion having tremor-dominant disease. Genetic analysis showed one parkin gene mutation. The limited knowledge on PD-causing genes and mutations in black populations warrants further studies involving next-generation sequencing approaches

Listerial brainstem encephalitis--treatable, but easily missed.

Listerial brainstem encephalitis (LBE) is an uncommon form of listerial central nervous system infection that progresses rapidly and is invariably fatal unless detected and treated early. We report on six adult patients with LBE, of whom five were managed or co-managed by our unit during the period January - June 2012. All presented with a short prodromal illness followed by a combination of brainstem signs, including multiple cranial nerve palsies with emphasis on the lower cranial nerves, ataxia, motor and sensory long-tract signs, a depressed level of consciousness and apnoea. In two cases the diagnosis was delayed with adverse outcomes. LBE may be difficult to diagnose: clinicians may not be aware of this condition, the brainstem location may not be recognised readily, general markers of inflammation such as the erythrocyte sedimentation rate, C-reactive protein level or white cell count may be normal, and the cerebrospinal fluid is typically normal or there are only mild and nonspecific findings. Serological tests are unreliable, and diagnosis is achieved through blood cultures, magnetic resonance imaging and clinical recognition.

Prophylactic sequential bronchoscopy after inhalation injury: results from a three-year prospective randomized trial.

OBJECTIVE: That the prophylactic, sequential use of bronchoscopy after inhalation injury as a therapeutic tool to remove secretions and carbonaceous material and to screen for the early detection of pneumonia will improve outcome. METHODS: A three-year prospective randomized trial at a regional burn center. RESULTS: Thirty-three patients with inhalation injury requiring mechanical ventilation were admitted over three years. The bronchoscopy group had a higher initial carboxyhemoglobin level at 11.9 % (95 % CI ± 9.6 %) versus the control group at 9.9 % (95 % CI ± 5.7 %, p = 0.7). There was no difference in the incidence of pneumonia between groups (p = 0.6). There was a trend toward fewer days of antibiotic use in the bronchoscopy group, at 4.5 days (95 % CI ± 4.5 days) versus 9.3 days (95 % CI ± 7.1 days, p = 0.3). Fewer patients were treated with antibiotics in the bronchoscopy group (4/13, 31 %) versus the control group (9/15, 60 %, p = 0.1). There was a statistically significant difference in the morbidity that favored the bronchoscopy group (3/13, 23 %) over the control group (9/15, 60 %, p = 0.04). There was no statistically significant difference between the two groups in days of mechanical ventilation (bronchoscopy 5.1 days, 95 % CI ± 3.6 days, control 6.7 days, 95 % CI ± 6.3 days, p = 0.7), ICU days (bronchoscopy 10 days, 95 % CI ± 10 days, control 18 days, 95 % CI ± 12 days, p = 0.4), and hospital days (bronchoscopy 21 days, 95 % CI ± 12 days, control 26 days, 95 % CI ± 12 days, p = 0.5), although the trends favored the bronchoscopy group for all of the endpoints. CONCLUSIONS: In conclusion, this program of scheduled, sequential bronchoscopy after inhalation injury showed several strong trends towards less morbidity, fewer days of mechanical ventilation, and a shorter length of stay. There was also a strong trend towards less antibiotic use and a shorter duration of treatment. This data is promising and should promote a larger, multi-institutional trial in the future.

Correlation of operative and pathological injury grade with computed tomographic grade in the failed nonoperative management of blunt splenic trauma.

BACKGROUND: Computed tomography (CT) is the standard for grading blunt splenic injuries, but the true accuracy, especially for grade IV or V injuries as compared to pathological findings, is unknown. STUDY DESIGN: A retrospective study from 2005 to 2011 was undertaken. RESULTS: There were 214 adults admitted with blunt splenic injury and 170 (79%) were managed nonoperatively. The remaining 44 patients (21%) required surgical intervention. There was a significant difference in the Injury Severity Score (ISS) between those who did and those who did not require splenectomy: median 31 (interquartile [IQ] range 11-51) versus 22 (IQ range 9-35, p = 0.0002). Ten patients presented in shock, had a positive ultrasound, and went to surgery. The remaining 34 had CT scans prior to surgery. Twenty-five (73%) had injury grades IV or V. The CT scan correctly graded the injury in 14 (41%) and was incorrect in 20 (59%). The assigned grade by the CT scan underestimated the true injury grade by one grade in six cases (30%), by two or more grades in nine (45%), and the CT images were obscured by blood and deemed "ungradeable" in five (25%). The CT scan was more accurate for grades I and II (100%) than for grades III-V (25-43%). The reasons for inaccuracy were either inability to visualize that the laceration involved the hilar vessels or excessive perisplenic blood which obscured the injury and/or the hilum. CONCLUSIONS: CT for splenic injury is accurate for grades I and II, but underestimates the true extent of injury for grades III-V. The reasons for the lack of correlation are the inability to determine hilar involvement and excessive perisplenic blood obscuring the injury. Patients with these image characteristics by CT scan should undergo splenectomy earlier if there are any signs of hemodynamic instability.

FAME 3: a novel form of progressive myoclonus and epilepsy.

BACKGROUND: Familial adult myoclonic epilepsy (FAME) is associated with myoclonus, tremor, and rare seizures, and is a nonprogressive disorder linked to the FAME 1 locus. A similar disorder has been linked to the FAME 2 locus. METHODS: Seventeen patients from two families with myoclonus and epilepsy were evaluated clinically and underwent EEG, EMG, jerk-locked averaging, and MRI scanning. Three had responses to magnetic stimulation assessed. Linkage was assessed for microsatellite markers across the FAME 1 and 2 loci. RESULTS: The median age at onset was 20 years, with many patients having frequent seizures, cognitive impairment, and cerebellar dysfunction. Electrophysiologic features of cortical myoclonus were typically present, but photosensitivity was uncommon. MRI frequently demonstrated cerebellar atrophy. Pathology of a single case showed Purkinje cell loss, dentate atrophy, and neuronal loss and gliosis in the olives and pallidum. Analysis of genotypes for markers at the FAME 1 and FAME 2 loci excluded these as the region containing the same locus in one family, but only the FAME 2 locus was excluded in the other family. CONCLUSIONS: This form of familial adult myoclonic epilepsy does not show linkage to either of the known familial adult myoclonic epilepsy loci, and is characterized in some members by frequent seizures, cerebellar ataxia, dementia, and progression of the disease. This may represent a new form of progressive myoclonus and epilepsy, which we have termed familial adult myoclonic epilepsy type 3.

Early pubertal female rats are more resistant than males to 6-hydroxydopamine neurotoxicity and behavioural deficits: a possible role for trophic factors.

PURPOSE: The infusion of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway in rats is commonly used to produce an animal model of Parkinson's disease (PD). However, most studies use male adult animals only. The present study focused on possible gender differences in vulnerability to 6-OHDA during the early pubertal period when the effects exerted by gonadal steroid hormones are unpronounced. METHODS: Young Sprague-Dawley rats, 35 days of age, were given a low vs. a higher dose of 6-OHDA in the medial forebrain bundle (MFB). Control rats received equivalent saline infusions. At 14 days post-surgery the rats were evaluated for forelimb akinesia. RESULTS: For the higher dose of 6-OHDA the female rats were less impaired than males in making adjustment steps in response to a weight shift and in a vibrissae-evoked forelimb placing test. Tyrosine hydroxylase (TH) immunoreactivity was significantly higher for the female rats. CONCLUSION: Early gender differences in cell survival factors and/or other promoters of neuroplasticity may have contributed to the beneficial outcome in the females. For example, NGF was found to be higher in the female rats following administration of DA neurotoxin. It is unclear whether gonadal steroids are involved, and if so, whether female hormones are protective or whether male hormones are prodegenerative. Determining the mechanisms for the improved outcome in the young female rats may lead to potential treatment strategies in PD.

Sediment TCDD-EQs and EROD and MROD activities in Ranid frogs from agricultural and nonagricultural sites in Michigan (USA).

In vitro studies have demonstrated atrazine-mediated induction of 7-ethoxyresorufin O-deethylase (EROD) activity. EROD is an enzyme active in the metabolism of many compounds, including many xenobiotics. These studies have suggested that atrazine may affect reproductive function by altering steroid metabolism. The goal of this study was to determine whether relationships could be detected between measured atrazine concentrations in surface waters and the liver-somatic index (LSI) and EROD and 7-methoxyresorufin O-deethylase (MROD) activities in the livers of ranid frogs. In addition, sediment dioxin toxic equivalents (TCDD-EQs) were determined using the H4IIE-luc cell bioassay. Adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana), and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south central Michigan in the summer of 2003. Atrazine concentrations at nonagricultural sites ranged from less than the limit of quantification (0.17 microg atrazine/L) to 0.23 microg atrazine/L and did not exceed 1.2 microg atrazine/L at agricultural sites. Sediment TCDD-EQs were measurable only at one agricultural site. Of the measured parameters, only LSI values in adult male frogs differed significantly between agricultural and nonagricultural sites, with greater values observed at agricultural sites. In green frogs, EROD and MROD activities were measurable in both adult and juvenile frogs and were similar among sites. Median EROD activities ranged from 13 to 21 pmol/min/mg protein in adult male green frogs and from 5 to 13 pmol/min/mg protein in adult female green frogs. Juvenile frogs had greater EROD and MROD activities than adult frogs. Bullfrogs and leopard frogs had greater activities than did green frogs. Atrazine concentrations were significantly and negatively correlated with MROD activity in adult male green frogs (Spearman R = -0.800). LSI and EROD and MROD activities of adult female or juvenile green frogs were not significantly correlated with atrazine concentrations. These results suggest that atrazine does not appear to have a consistent association with EROD or MROD activities in wild-caught green frogs.

Plasma steroid hormone concentrations, aromatase activities and GSI in ranid frogs collected from agricultural and non-agricultural sites in Michigan (USA).

The triazine herbicide atrazine has been hypothesized to disrupt sexual development in frogs by up-regulating aromatase activity, resulting in greater estradiol (E2) concentrations and causing feminization in males. The goal of this study was to collect native ranid frogs from atrazine-exposed ponds and determine whether relationships exist between measured atrazine concentrations and the gonadosomatic index (GSI), plasma concentrations of testosterone (T), E2 or 11-ketotestosterone (KT), or with aromatase activity. In the summer of 2002 and 2003, adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south-central Michigan. Atrazine concentrations were below the limit of quantification at non-agricultural sites. Atrazine concentrations did not exceed 2 microg/L at most agricultural sites, but a concentration of 250 microg atrazine/L was measured in one sample from one site in 2002. Plasma steroid concentrations varied among locations. Aromatase activity was measurable in less than 11% of testes in adult males, and in less than 4% of testes in juvenile males. Median aromatase activities in ovaries of adult females ranged from 3 to 245 pmol/h/mg protein, and maximum activities were 2.5-fold greater in juveniles than in adults. Atrazine concentrations were not significantly correlated with any of the parameters measured in this study. These results indicate that atrazine does not up-regulate aromatase in green frogs in the wild, and does not appear to affect plasma steroid hormone concentrations.

Atrazine concentrations, gonadal gross morphology and histology in ranid frogs collected in Michigan agricultural areas.

The triazine herbicide atrazine has been suggested to be a potential disruptor of normal sexual development in male frogs. The goals of this study were to collect native ranid frogs from sites in agricultural and non-agricultural areas and determine whether hypothesised atrazine effects on the gonads could be observed at the gross morphological and histological levels. Juvenile and adult green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and leopard frogs (R. pipiens) were collected in the summers of 2002 and 2003. Atrazine concentrations were below the limit of quantification at non-agricultural sites, and concentrations did not exceed 2 microg/L at most agricultural sites. One concentration greater than 200 microg atrazine/L was measured once at one site in 2002. Hermaphroditic individuals with both male and female gonad tissue in either one or both gonads, were found at a low incidence at both non-agricultural and agricultural sites, and in both adults and juveniles. Testicular oocytes (TO) were found in male frogs at most of the sites, with the greatest incidence occurring in juvenile leopard frogs. TO incidence was not significantly different between agricultural and non-agricultural sites with the exception of juveniles collected in 2003. Atrazine concentrations were not significantly correlated with the incidence of hermaphroditism, but maximum atrazine concentrations were correlated with TO incidence in juvenile frogs in 2003. However, given the lack of a consistent relationship between atrazine concentrations and TO incidence, it is more likely the TOs observed in this study result from natural processes in development rather than atrazine exposure.

Seasonal exposures to triazine and other pesticides in surface waters in the western Highveld corn-production region in South Africa.

The objective of this study was to characterize concentrations of atrazine, terbuthylazine, and other pesticides in amphibian habitats in surface waters of a corn-production area of the western Highveld region (North-West Province) of South Africa. The study was conducted from November 2001 to June 2002, coinciding with the corn-production season. Pesticide residues were measured at regular intervals in surface water from eight ponds, three in a non-corn-growing area (NCGA) and five within the corn-growing area (CGA). Measured atrazine concentrations differed significantly among sites and between samples. In the five CGA sites, the maximum atrazine concentrations measured during the study ranged from 1.2 to 9.3 microg/L. Although no atrazine was recorded as being applied in the catchment of the three NCGA sites, maximum concentrations from 0.39 to 0.84 microg/L were measured during the study, possibly as a result of atmospheric transport. Maximum measured concentrations of terbuthylazine ranged from 1.22 to 2.1 microg/L in the NCGA sites and from 1.04 to 4.1 microg/L in the CGA sites. The source of terbuthylazine in the NCGA sites may have been in use other than in corn. The triazine degradation products, deisopropylatrazine (DIA) and deethylatrazine (DEA) and diaminochlorotriazine (DACT) were also found in water from both the CGA and NCGA sites. Concentrations of DIA were > or = 1 microg/L throughout the season, while DEA concentrations were mostly <0.5 microg/L before planting but increased after planting and application of herbicides to concentrations >2 microg/L in some locations. Concentrations of DACT were highly variable (LOD to 8 microg/L) both before and after planting and application, suggesting that they resulted from historical use of triazines in the area. Other herbicides such as simazine and acetochlor were only detected infrequently and pesticides such as S-metolachlor, cypermethrin, monocrotophos, and terbuphos, known to be used in the CGA, were not detected in any of the samples. Because of dilution by higher than normal rainfall in the study period, these concentrations may not be predictive of those in years of normal rainfall.

The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo.

Oseltamivir carboxylate is a potent and specific inhibitor of influenza A and B neuraminidase (NA). Oseltamivir phosphate, the ethyl ester prodrug of oseltamivir carboxylate, is the first orally active NA inhibitor available for the prophylaxis and treatment of influenza A and B. It offers an improvement over amantadine and rimantadine which are active only against influenza A and rapidly generate resistant virus. The emergence of virus resistant to oseltamivir carboxylate in the treatment of naturally acquired influenza infection is low (about 1%). The types of NA mutation to arise are sub-type specific and largely predicted from in vitro drug selection studies. A substitution of the conserved histidine at position 274 for tyrosine in the NA active site has been selected via site directed mutagenesis, serial passage in culture under drug pressure in H1N1 and during the treatment of experimental H1N1 infection in man. Virus carrying H274Y NA enzyme selected in vivo has reduced sensitivity to oseltamivir carboxylate. The replicative ability in cell culture was reduced up to 3 logs, as was infectivity in animal models of influenza virus infection. Additionally, pathogenicity of the mutant virus is significantly compromised in ferret, compared to the corresponding wild type virus. Virus carrying a H274Y mutation is unlikely to be of clinical consequence in man.

Distribution of neuronal melanocortins in the spadefoot toad Spea multiplicata and effects of stress.

We examined the effects of an acute stressor on regional alpha-melanocyte-stimulating hormone (alphaMSH) content in the New Mexican spadefoot toad, Spea multiplicata. We first used immunocytochemistry along with radioimmunoassay (RIA) to examine the distribution of pro-opiomelanocortin (POMC) neurons in the brain of Spea. Neurons immunoreactive for alphaMSH, beta-endorphin, and corticotropin were observed in the preoptic nucleus and ventral infundibulum of the hypothalamus. Ascending immunoreactive fibers projected to the olfactory nucleus, nucleus accumbens, and striatum. Numerous immunoreactive fibers were also observed in the hypothalamus. The thalamus/hypothalamus (T/HT) contained the greatest concentrations of alphaMSH as determined by RIA followed by the preoptic area (PO). Levels in the telencephalon, brain stem, and optic tectum (OT) were 14-23 times lower than in the T/HT. Exposure to a brief stressor elevated alphaMSH levels in the PO and OT. We conclude that Spea possesses two distinct POMC neuronal cell groups, one located in the anterior preoptic area and one located in the ventral infundibulum. Ascending projections to the basal ganglia might play an indirect role in tectal regulation and the control of prey-catching behavior. Exposure to an acute stressor alters brain alphaMSH content in Spea, although there are regional and temporal differences in the response pattern compared to Bufo. These findings are consistent with the notion that neuronal melanocortins influence how frogs and toads gather information about their environment during stress.

Further evidence of joint time-place control of rats' behavior: results from an 'open hopper' test.

Rats were trained on an interval time-place task. Food was intermittently available on each of four levers for 4 min in a 16-min session. After baseline training the rats received 'open hopper' sessions in which food was available on all levers for all of the 16-min sessions. Despite the absence of any contingencies for doing so, the rats continued to press the levers in the 'correct' sequence, for roughly the 'correct' amount of time. This confirms that the rat behavior was controlled, in part, by a representation of an elapsed interval of time. The rats responding was more variable in 'open hopper' sessions and error increased (in an exponential fashion) as the session proceeded. This finding suggests that the rats may have used shifts in the location of food availability to minimize the accumulation of error throughout baseline sessions.

Primary venorrhaphy for traumatic inferior vena cava injuries.

Primary venorrhaphy for traumatic inferior vena cava (IVC) injury has been criticized because of the potential for stenosis, thrombosis, and embolism. A retrospective study was performed to evaluate the morbidity and outcome of this method. Thirty-eight patients at our institution had traumatic injuries to the IVC between 1994 and 1999. Thirty (79%) were from firearms, five (13%) from stab wounds, and three (8%) from blunt trauma. Six patients died in the emergency department. The remaining 32 patients underwent exploratory celiotomy with 23 survivors and nine intraoperative deaths for a mortality rate of 28 per cent (nine of 32). Vascular control was achieved by manual compression in 44 per cent and by local clamping directly above and below the injury in 38 per cent. All repairs were by primary venorrhaphy, and no patient was treated with patch angioplasty or venous reconstruction. Three patients had caval ligation. Follow-up IVC imaging in 11 patients revealed that the IVC was patent in eight, narrowed in two, and thrombosed below the renal veins in one. One patient developed a pulmonary embolus. The vast majority of traumatic injuries to the IVC can be managed by direct compression or local clamping and primary venorrhaphy. Direct repairs are associated with a low thrombosis and embolic complication rate.

The association of HER-2/neu amplification with breast cancer recurrence.

HYPOTHESIS: Amplification of the HER-2/neu oncogene in 25% of breast cancers is associated with a shortened disease-free survival. DESIGN: Retrospective analysis of a patient population referred to a tertiary care facility for HER-2/neu testing. The mean follow-up was 56 months. SETTING: Large, urban, tertiary care hospital. PATIENTS: From 1995 to 1999, a consecutive sample of 190 patients with breast cancer had tissue samples tested for overexpression of the cell surface oncoprotein by immunostaining (IM) or amplification of the HER-2/neu oncogene by fluorescence in situ hybridization or both. Forty-nine subjects were excluded because they had tissue samples tested at our institution but received their treatment elsewhere. All patients tested for HER-2/neu after diagnosis with breast cancer in 1999 (n = 47) were excluded from analysis because of short follow-up time. One patient was excluded who had in situ ductal carcinoma. The remaining 93 patients were analyzed. RESULTS: Of 93 patients, 40 (43%) had gene amplification. Overall, patients with oncogene amplification had a shorter median disease-free interval (22 months) compared with controls (40 months) (P =.003). Analysis by the Cox regression model showed that the HER-2/neu status remained significantly associated with time to relapse even after adjusting for age and tumor grade (P =.002; adjusted relative risk, 2.4; 95% confidence interval, 1.4-4.4). No association was found between gene amplification and tumor grade (P =.98), estrogen/progesterone receptor status (P = .29 and P = .43, respectively), or lymph node status (P = .98). Seventy-two patients (77%) eventually had disease recurrence, with 18 (25%) of these recurring locally. CONCLUSIONS: The HER-2/neu oncogene is an independent prognostic indicator of a subset of breast cancers that are at high risk of early recurrence, regardless of tumor grade, estrogen/progesterone receptor status, and lymph node status. Patients amplifying the HER-2/neu oncogene have a shorter disease-free survival than patients without the oncogene.