Linda S. Hynan

Acetaminophen‐induced acute liver failure: Results of a United States multicenter, prospective study

Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen‐induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6‐year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen‐related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra‐strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic‐containing compounds. Eighty‐one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant‐free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high‐risk use settings is recommended. (HEPATOLOGY 2005;42:1364–1372.)

A total score for the CERAD neuropsychological battery

Objective: To develop a total or composite score for the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery. Method: CERAD total scores were obtained by summing scores from the individual CERAD subtests (excluding the Mini-Mental State Examination [MMSE]) into a total composite (maximum score = 100). The method of tabulating the total score was constructed using normal controls (NCs; n = 424) and patients with AD (n = 835) from the CERAD registry database. The utility of the total score was further tested in independent samples of mild AD (n = 95), mild cognitive impairment (MCI; n = 60), and NC (n = 95) subjects. Results: The CERAD total score was highly accurate in differentiating NC and AD subjects in the CERAD registry. Age, gender, and education effects were observed, and demographic correction scores were derived through multiple regression analysis. Demographically corrected CERAD total scores showed excellent test-retest reliability across samples (r = 0.95) and were highly correlated with the MMSE (r = 0.89) and Clinical Dementia Rating Scale (r = −0.83) in mixed AD and NC samples and with the Blessed Dementia Rating Scale in an AD sample (r = −0.40). The CERAD total score was highly accurate in differentiating independent samples of NC, MCI, and AD subjects. Conclusion: Results provide support for the validity of a Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) total score that can be used along with the normative data to provide an index of overall level of cognitive functioning from the CERAD neuropsychological battery.

Factors related to hydrocephalus after aneurysmal subarachnoid hemorrhage.

OBJECTIVEThe purpose of this study was to identify factors predictive of shunt-dependent hydrocephalus among patients with aneurysmal subarachnoid hemorrhage. The data can be used to predict which patients in this group have a high probability of requiring permanent cerebrospinal fluid diversion. METHODSSeven hundred eighteen patients with aneurysmal subarachnoid hemorrhage who were treated between 1990 and 1999 were retrospectively studied, to identify factors contributing to shunt-dependent hydrocephalus. With these data, a stepwise logistic regression procedure was used to determine the effect of each variable on the development of hydrocephalus and to create a scoring system. RESULTSOverall, 152 of the 718 patients (21.2%) underwent shunting procedures for treatment of hydrocephalus. Four hundred seventy-nine of the patients (66.7%) were female. Of the factors investigated, the following were associated with shunt-dependent hydrocephalus, as determined with a variety of statistical methods: 1) increasing age (P < 0.001), 2) female sex (P = 0.015), 3) poor admission Hunt and Hess grade (P < 0.001), 4) thick subarachnoid hemorrhage on admission computed tomographic scans (P < 0.001), 5) intraventricular hemorrhage (P < 0.001), 6) radiological hydrocephalus at the time of admission (P < 0.001), 7) distal posterior circulation location of the ruptured aneurysm (P = 0.046), 8) clinical vasospasm (P < 0.001), and 9) endovascular treatment (P = 0.013). The presence of intracerebral hematomas, giant aneurysms, or multiple aneurysms did not influence the development of shunt-dependent hydrocephalus. CONCLUSIONThe results of this study can help identify patients with a high risk of developing shunt-dependent hydrocephalus. This may help neurosurgeons expedite treatment, may decrease the cost and length of hospital stays, and may result in improved outcomes.

Emergency Surgery for Colon Carcinoma

AbstractPURPOSE: Emergency surgery for colon cancer is widely thought to be associated with increased likelihood of surgical morbidity and mortality; however, other coexistent factors such as advanced disease, the age of the patient, and medical comorbid conditions may also influence these outcomes. The primary purpose of this study was to identify the relative risk for surgical morbidity and/or mortality conferred by emergency surgery compared with elective surgery for patients with colon cancer. nMETHODS: An Institutional Review Board-approved, case-control study was performed. During the period from January 1, 1995, to June 30, 2001, a total of 184 primary surgeries for colon cancer were performed. Emergency indications for surgery were defined as peritonitis, intra-abdominal abscess, or complete bowel obstruction at presentation (defined as emesis, distention on examination, and confirmatory plain radiograph films). By this definition, 29 patients (15.7 percent) met the criteria for inclusion. These patients were age and stage matched with 29 patients derived from the remaining 155 patients. Information was collected on surgical morbidity and mortality, length of stay, and survival. nRESULTS: Age, medical comorbidities, and stage of disease were well matched between groups. The indications for the 29 emergency surgeries were as follows: 6 for peritonitis, 2 for abscesses, and 21 for complete obstructions. Nine patients did not have their primary tumor removed. Sixteen patients underwent resection and anastomosis; the remaining four patients underwent a Hartmann’s procedure. Overall surgical morbidity (64 vs. 24 percent; odds ratio, 5.1; 95 percent confidence interval, 1.7–16) and mortality (34 vs. 7 percent; odds ratio, 7.1; 95 percent confidence interval, 1.4–36.2) were significantly higher for patients undergoing emergency surgery. Among patients surviving surgery, there was no difference in overall survival between patients undergoing emergency compared with elective operation. nCONCLUSIONS: Emergency surgery has a strong negative influence (beyond that which is expected based on stage of disease) on immediate surgical morbidity and mortality. The similarity between the two groups in overall survival for patients surviving the perioperative period suggests that the negative impact of emergency surgery is confined to the immediate postoperative period.

Aneusomy 17 in Breast Cancer: Its Role in HER-2/neu Protein Expression and Implication for Clinical Assessment of HER-2/neu Status

HER-2/neu protein overexpression in breast cancer is mostly caused by HER-2/neu gene amplification. However, it is unclear whether aneusomy 17 may also play a role. Using immunohistochemistry assay (IHC) with DAKO antibody and manual quantitation, 189 specimens were selected from archival invasive breast cancer specimens, including most IHC-positive and some IHC-negative cases (n = 158 and 31, respectively). They were then analyzed by PathVysion fluorescence in situ hybridization (FISH) assay (Vysis, Inc., Downers Grove, IL) and by an image analyzer (ACIS; ChromaVision Medical Systems, Inc., San Juan Capistrano, CA)–assisted IHC quantitation. Ninety-two cases contained disomy 17 (chromosome 17 centromere, 1.76–2.25 signals per cell) whereas 97 cases had aneusomy 17, including 82 with low polysomy (2.26–3.75 signals per cell), 10 with high polysomy (≥3.76 signals per cell), and 5 with hypodisomy (≤1.75 signals per cell). HER-2/neu protein expression had the highest correlation with HER-2/neu gene dosage (copy number; r = .826), followed by the HER-2/neu gene to chromosome 17 ratio (r = .733). The lowest correlation was with the chromosome 17 copy number (r = .307), on which the 10 cases with high polysomy 17 had a disproportionately high impact. The FISH assay using the PathVysion criterion for HER-2/neu gene amplification (HER-2/neu gene to chromosome 17 ratio, ≥2.00) achieved higher concordance with ACIS IHC than did an alternative FISH criterion (absolute HER-2/neu gene copy number, ≥4.00 signals per cell). Most ACIS IHC-PathVysion FISH–discordant cases contained disomy or low polysomy 17, whereas all 10 cases with high polysomy 17 had no such discordance. However, two cases with monosomy 17 had ACIS IHC-PathVysion FISH discordance, i.e., with gene amplification, but no protein overexpression. Both cases would have had no gene amplification if the alternative FISH criterion had been used. In conclusion, aneusomy 17 is common in breast cancer. Except in a certain subset of cases, aneusomy 17 probably is not a significant factor for HER-2/neu protein expression or for clinical assessment of HER-2/neu status.

Is routine cholecystectomy required during laparoscopic gastric bypass

Background: Routine cholecystectomy is often performed at the time of gastric bypass for morbid obesity. The aim of our study was to determine the incidence of gallstone formation requiring cholecystectomy following a laparoscopic Roux-en-Y gastric bypass (LRYGBP). Methods: 289 LRYGBP were performed between November 1999 and May 2002. 60 patients (21%) who had prior cholecystectomy were excluded. If gallstones were identified by intra-operative ultrasound (IOUS), simultaneous cholecystectomy was performed. Patients without gallstones were prescribed ursodiol for 6 months and scheduled for follow-up with transabdominal ultrasound. Results: During LRYGBP, gallstones were detected in 40 patients using IOUS (14%) and simultaneous cholecystectomy was performed. Of 189 patients with no stones identified by IOUS, 151 patients (80%) had a postoperative ultrasound after 6 months. 39 patients developed gallstones (22%) and 12 developed sludge (8%), as demonstrated by ultrasound at the time of follow-up. 11 patients had gallstone-related symptoms and subsequently underwent cholecystectomy (7%). 106 patients (70%) were gallstone-free at the time of ultrasound follow-up. Ursodiol compliance was found to be significantly lower for patients developing stones than for gallstone-free patients (38.9% vs 58.3%, z =-2.00, P = 0.045). Conclusions: There is a low incidence of symptomatic gallstones requiring cholecystectomy after LRYGBP. Prophylactic ursodiol is protective. Routine IOUS and selective cholecystectomy with close patient follow-up is a rational approach in the era of laparoscopy.

Platelet amyloid precursor protein processing: A bio-marker for Alzheimer's disease

The amyloid precursor protein (APP) in brain is processed either by an amyloidogenic pathway by beta-secretase and gamma-secretase to yield Abeta (beta-amyloid 4 kDa) peptide or by alpha-secretase within the beta-amyloid domain to yield non-amyloidogenic products. We have studied blood platelet levels of a 22-kDa fragment containing the Abeta (beta-amyloid 4 kDa) peptide, beta-secretase (BACE1), alpha-secretase (ADAM10), and APP isoform ratios of the 120-130 kDa to 110 kDa peptides from 31 Alzheimers disease (AD) patients and 10 age-matched healthy control subjects. We found increased levels of Abeta4, increased activation of beta-secretase (BACE1), decreased activation of alpha-secretase (ADAM10) and decreased APP ratios in AD patients compared to normal control subjects. These observations indicate that the blood platelet APP is processed by the same amyloidogenic and non-amyloidogenic pathways as utilized in brain and that APP processing in AD patients is altered compared to control subjects and may be a useful bio-marker for the diagnosis of AD, the progression of disease and for monitoring drug responses in clinical trials.

Dyadic short forms of the Wechsler Adult Intelligence Scale-III.

Various short forms of the Wechsler Adult Intelligence Scale (WAIS)/WAIS-R have been developed to obtain estimates of overall intellectual level, although little research of WAIS-III short forms has been published to date. Full Scale IQ (FSIQ) estimates from four WAIS-III dyadic short forms were obtained by entering selected subtest scores from a mixed neurologic/psychiatric sample (n = 196) into regression equations. Results were cross validated on a second sample (n = 57). Within both samples, WAIS-III FSIQ scores were highly correlated (r = .90-.92, p < .001) with estimated FSIQ scores. Estimated FSIQ fell within 5 points of actual FSIQ in 49% to 74% of cross-validation cases and within 10 points of actual FSIQ in 81% to 93% of the sample. Comparable to findings from previous short-form investigations, actual and estimated FSIQ classification levels agreed in 46% to 67% of cases in the cross-validation sample. These dyadic WAIS-III forms appear appropriate for obtaining gross estimates of FSIQ in similar populations, although caution is recommended in interpreting estimated IQ scores.

Subscores of the FAB differentiate frontotemporal lobar degeneration from AD

Objective: To determine the clinical utility of the Frontal Assessment Battery (FAB), a short test of frontal lobe functions, in differentiating frontotemporal lobar degeneration (FTLD) from Alzheimer disease (AD). Methods: FAB total scores and subscores for 23 subjects with FTLD and 31 subjects with AD were compared for sensitivity, specificity, and positive predictive value. Concurrent validity of the FAB with the Mini-Mental State Examination (MMSE) and other scales was also assessed. Results: The FAB did not have positive predictive value for FTLD. Total FAB scores did not differ between the FTLD and AD groups. However, three subtests of the FAB (mental flexibility, motor programming, and environmental autonomy) demonstrated significant differences between the two groups. Total FAB scores correlated with scores on the MMSE, a more general test of cognition. Conclusion: The Frontal Assessment Battery did not discriminate subjects with frontotemporal lobar degeneration from those with Alzheimer disease, though certain subtests may be helpful in differential diagnosis.

Effectiveness of a graduate medical education program for improving medical event reporting attitude and behavior

Objectives: To evaluate the effectiveness of an educational program for improving medical event reporting attitude and behavior in the ambulatory care setting among graduate medical trainees. Design: One group pre- and post-test study. Setting: The University of Texas Southwestern Medical Center at Dallas Family Medicine Residency Program. Participants: All family practice residents (nu200a=u200a30). Intervention: Patient safety educational program implemented through an introductory lecture and 6 monthly conferences, June to December 2002, involving medical events that occurred in the ambulatory care setting. Outcome measures: Medical event reporting attitude and behavior at baseline and at 6 month follow up, and barriers to medical event reporting at the 6 month follow up. Results: Program attendance was significantly correlated with medical event reporting attitude and behavior change (rhou200a=u200a0.525, pu200a=u200a0.003). The median change in medical event reporting attitude and behavior was zero and not statistically significant (pu200a=u200a0.566). Major barriers to medical event reporting were lack of time, extra paper work, and concern about career and personal reputation. Conclusions: Attending the patient safety educational program was key for promoting a positive medical event reporting attitude and behavior change among graduate trainees. Major barriers to medical event reporting were lack of time, extra paper work, and concern about career and personal reputation. Future research will need to focus on reducing these barriers and to evaluate the effectiveness of such a program over longer periods of time, since making a positive change in medical event reporting attitude and behavior must be made at the individual and organizational levels.