Validity of the Veterans Health Administration's traumatic brain injury screen

Belanger HG, Vanderploeg RD, Soble JR, Richardson M, Groer S. Validity of the Veterans Health Administration's traumatic brain injury screen.ObjectiveTo compare the results of Veterans Affairs' (VA's) initial traumatic brain injury (TBI) Clinical Reminder Screen with the more extensive second-level Comprehensive TBI Evaluation in a national sample.DesignCriterion-standard.SettingVeterans Health Administration system of polytrauma care.ParticipantsThe data were from VA's centralized database Patient Care Services on the TBI Clinical Reminder Screen and Comprehensive TBI Evaluation results of veterans (N=48,175).InterventionsNone.Main Outcome MeasuresSensitivity, specificity, positive predictive value, and negative predictive value of the TBI Clinical Reminder Screen were calculated by using the Comprehensive TBI Evaluation findings as the comparative standard for TBI confirmation.ResultsThe TBI Clinical Reminder Screen has generally good sensitivity (.87–.90) but poor specificity (.13–.18). In addition, the TBI Clinical Reminder Screen, when compared with the Comprehensive TBI Evaluation by a clinician, has generally poor negative predictive power (.31–.49) in this sample. However, negative predictive power is good with an estimated Veterans Health Administration system-wide TBI prevalence rate of 15% (.89). Positive predictive power was acceptable (.77) in this sample. The screen performs comparably across patient demographic and symptom severity characteristics, as well as across level of polytrauma care. Systematic evaluations by clinicians primarily reveal mental health–perceived causes of ongoing symptoms.ConclusionsIn summary, VA's Clinical Reminder Screen, when evaluated against the follow-up Comprehensive TBI Evaluation, has good sensitivity but poor specificity.     

Mitomycin C skin toxicity studies in mice: reduced ulceration and altered pharmacokinetics with topical dimethyl sulfoxide

A series of toxicologic and pharmacokinetic studies were performed in BALB/c mice administered intradermal (ID) mitomycin C (MMC) at doses of .015 to 0.25 mg. Dose-dependent skin ulcers were produced at clinically relevant MMC dose levels of .05 and .075 mg (3.6 to 10.7 mg/m2). These doses produced peak ulcers of 0.15 to 0.22 cm2, respectively, one to five days after injection. The integrated ulcer area X time values (area under the curve [AUC] ulceration) were 0.89 and 3.11 cm2 X d. A large number of local pharmacologic adjuvants were found to be ineffective at reducing MMC ulceration after proximal ID injection. These included diphenhydramine, catalase, heparin, hyaluronidase, hydrocortisone, cysteine, N-acetylcysteine, lidocaine, vitamin E, and superoxide dismutase. Also, neither topical heating nor cooling of skin reduced MMC ulcerations. In contrast, a single topical application of a 100% dimethyl sulfoxide (DMSO) solution completely prevented 0.025 mg MMC-induced skin ulceration and significantly reduced .075 mg MMC ulceration (P less than .05 by multiple range tests). Topical DMSO also altered the disposition of ID MMC in mouse skin but not in plasma. Unexpectedly, the DMSO applications slowed MMC elimination from the skin. DMSO significantly increased the AUC for MMC in skin from 0.89 to 2.25 ng/h/mL of tissue (P less than .05). DMSO did not alter the degree of protein binding in skin tissue nor the in vitro chemical stability of MMC in skin tissue homogenates. These results show that experimental MMC-induced skin ulcers in mice can be ameliorated with an immediate application of topical DMSO. This effect is not due to enhanced systemic drug uptake, but may be due to reduced reactivity of MMC with target cellular nucleophiles.     

Ammonium acid urate calculi: a reevaluation of risk factors

PURPOSE: We reevaluate the demographic and metabolic risk factors for ammonium acid urate stones. MATERIALS AND METHODS: Since 1986, 23 women and 21 men ranging in age from 20 to 81 years (mean 48.7) were treated for stones partly composed of ammonium acid urate. Stone composition ranged from 2 to 60% ammonium acid urate (mean 24.1) of the total stone mass. No patient had a pure ammonium acid urate stone, although 11 (25%) had stones with ammonium acid urate as the predominant crystal. RESULTS: In the 44 patients 1 or more potential risk factors for ammonium acid urate were identified. Of the patients 11 (25%) had a history of inflammatory bowel disease with 10 (22.7%) having undergone ileostomy diversion, 6 (13.6%) admitted to a history of significant laxative use or abuse, 18 (40.9%) were morbidly obese, 16 (36.4%) had a history of recurrent urinary tract infections and 9 (20.5%) had a history of recurrent uric acid stones. CONCLUSIONS: Patients clearly at risk for stones with an ammonium acid urate component include those with a history of inflammatory bowel disease and ileostomy diversion or laxative abuse. Other factors that may potentially enhance ammonium acid urate stone formation include morbid obesity, recurrent uric acid calculi and recurrent urinary tract infection. A careful history followed by further metabolic evaluation is warranted in these patients.     

The effect of perceptual reasoning abilities on confrontation naming performance: An examination of three naming tests

Introduction: Confrontation naming tests are a common neuropsychological method of assessing language and a critical diagnostic tool in identifying certain neurodegenerative diseases; however, there is limited literature examining the visual–perceptual demands of these tasks. This study investigated the effect of perceptual reasoning abilities on three confrontation naming tests, the Boston Naming Test (BNT), Neuropsychological Assessment Battery (NAB) Naming Test, and Visual Naming Test (VNT) to elucidate the diverse cognitive functions underlying these tasks to assist with test selection procedures and increase diagnostic accuracy. Method: A mixed clinical sample of 121 veterans were administered the BNT, NAB, VNT, and Wechsler Adult Intelligence Scale–4th Edition (WAIS–IV) Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) as part of a comprehensive neuropsychological evaluation. Results: Multiple regression indicated that PRI accounted for 23%, 13%, and 15% of the variance in BNT, VNT, and NAB scores, respectively, but dropped out as a significant predictor once VCI was added. Follow-up bootstrap mediation analyses revealed that PRI had a significant indirect effect on naming performance after controlling education, primary language, and severity of cognitive impairment, as well as the mediating effect of general verbal abilities for the BNT (B = 0.13; 95% confidence interval, CI [.07, .20]), VNT (B = 0.01; 95% CI [.002, .03]), and NAB (B = 0.03; 95% CI [.01, .06]). Conclusions: Findings revealed a complex relationship between perceptual reasoning abilities and confrontation naming that is mediated by general verbal abilities. However, when verbal abilities were statistically controlled, perceptual reasoning abilities were found to have a significant indirect effect on performance across all three confrontation naming measures with the largest effect noted with the BNT relative to the VNT and NAB Naming Test.     

Pilot Study Using a Humanized CC49 Monoclonal Antibody (HuCC49°C<Subscript>H</Subscript>2) to Localize Recurrent Colorectal Carcinoma

Background: CC49 is a monoclonal antibody directed against a pancarcinoma antigen (TAG-72) expressed by colorectal cancers. The use of murine CC49 in radioimmunoguided surgery (RIGS) was problematic because of the human anti-mouse antibodies (HAMA) generated. This study was designed to assess the clearance, safety, and effectiveness of localization of a complimentarity determining region (CDR)-grafted humanized domain-deleted antitumor CC49 antibody (HuCC49°C_H2).Methods: After thyroid blockade, 1 mg of HuCC49°C_H2 radiolabeled with 2 mCi of iodine-125 was administered. All patients subsequently underwent traditional exploration followed by a survey with the gamma-detecting probe. In five patients, exploration was performed 10 to 24 days after injection, when precordial counts were sufficiently low (<30 counts per 2 seconds [cp2s]). Traditionally suggestive and probe-positive tissue was biopsied or excised and examined for the presence of carcinoma, when considered appropriate by the operating surgeon. Serum was assessed for HAMA.Results: Seventeen sites were identified as suggestive of carcinoma on traditional exploration and 21 by RIGS. Of these, pathologic correlation was obtained in 15. The sensitivity of RIGS was 92%, and the positive predictive value was 100%. None of the patients expressed significant HAMA.Conclusions: This initial study indicates that the HuCC49°C_H2 monoclonal antibody, when used with RIGS, is safe and sensitive in detecting recurrent intra-abdominal colon cancer.     

Correlative Whole-Body FDG-PET and Intraoperative Gamma Detection of FDG Distribution in Colorectal Cancer

Purpose: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is the superior imaging modality for detection of primary and recurrent colorectal cancer compared to magnetic resonance imaging (MRI) or computerized tomography (CT). We investigated the feasibility of developing intraoperative procedures for detection of FDG in tumor deposits in order to assist the surgeon in achieving an optimal reduction of tumor burden.Procedures: Fourteen patients (45-83 years of age) were scanned using FDG-PET followed by Gamma Detection Probe evaluation at laparotomy. One patient did not have a pre-operative FDG-PET scan. The collimated detector probe contained a CdZnTe crystal (7mm diameter x 2mm thick). We used a lower window setting of 200 KeV and an open upper window setting. Fasted patients were given an IV bolus of FDG (4.0-5.7 mCi) 15-20 minutes prior to preparation for surgery. Catheterization and the diuretic Lasix were used to remove FDG activity from the bladder. The time from FDG injection to intraoperative GDP data acquisition varied from 58-110 minutes.Results: In all patients, the GDP detected background activity in normal tissues (aorta, colon, liver, kidney, abdominal wall, mesentery, and urinary bladder). The GDP correctly identified single or multiple tumor foci in 13/14 patients as noted by an audible signal from the control unit (3 S.D. above counts obtained from normal tissues). These tumor foci corresponded to regions of high FDG uptake as seen on FDG-PET scans. The one case that the GDP did not localize was a recurrent mucin pseudomyxoma-producing tumor (acellular, mucinous deposits). Ex vivo GDP evaluations demonstrated significant tumor:normal adjacent tissue activity (audible signals in 6/6 tumor samples tested).Conclusions: These data demonstrate that tumors identified from pre-operative whole-body PET scans can be localized during surgery utilizing a gamma probe detector and FDG.