Importance of the physical exam: double-blind randomized controlled trial of radiologic interpretation of ventral hernias after selective clinical information.

PURPOSE: Increasingly, radiologic imaging is obtained as part of the pathway in diagnosing ventral hernias. Often, radiologists receive incomplete or incorrect clinical information from clinicians. OBJECTIVE: The aim of the study is to determine if clinical exam findings alter radiological interpretation of ventral hernias on CT. METHODS: This is a single-institution double-blind, randomized trial. All patients with a recent abdominal/pelvic CT scan seen in various surgical clinics were enrolled. A surgeon blinded to the CT scan findings performed a standardized physical examination and assessed for the presence of a ventral hernia. Seven independent radiologists blinded to the study design reviewed the scans. Each radiologist received one of three types of clinical exam data per CT: accurate (correct), inaccurate (purposely incorrect), or none. Allocation was random and stratified by the presence of clinical hernia. The primary outcome was the proportion of radiologic hernias detected, analyzed by chi square. RESULTS: 115 patients were enrolled for a total of 805 CT scan reads. The proportion of hernias detected differed by up to 25% depending on if accurate, no, or inaccurate clinical information was provided. Inaccurate clinical data in patients with no hernia on physical exam led to a significant difference in the radiologic hernia detection rate (54.3% versus 35.7%, p = 0.007). No clinical data in patients with a hernia on physical exam led to a lower radiologic hernia detection rate (75.0% versus 93.8%, p = 0.001). CONCLUSIONS: The presence and accuracy of clinical information provided to radiologists impacts the diagnosis of abdominal wall hernias in up to 25% of cases. Standardization of both clinical and radiologic examinations for hernias and their reporting are needed. TRIAL REGISTRATION: Clinicaltrials.gov, Number NCT03121131, https://clinicaltrials.gov/ct2/show/NCT03121131.

Detection of cardiac transplant rejection with 111In-labeled lymphocytes and gamma scintigraphy.

BACKGROUND: Cardiac transplantation is an increasingly important treatment for patients with end-stage heart failure. Rejection is one of the major limitations, and currently, serial endomyocardial biopsies are required to diagnose rejection. In the year after transplantation, patients routinely undergo 12, 14, or more biopsies. Infiltration of lymphocytes into the graft is a central feature of rejection. Previous studies from our laboratory have demonstrated the feasibility of detecting early rejection noninvasively with gamma scintigraphy after administration of autologous lymphocytes labeled with 111In. METHODS AND RESULTS: Eight patients were studied at the time of routine biopsy an average of 4.5 months after cardiac transplantation. Autologous lymphocytes were isolated and labeled with 111In. Forty-eight to 72 hours later, patients underwent planar scintigraphic imaging. Myocardial accumulation of labeled lymphocytes was quantified (indium excess, IE) with a previously described and validated technique. Animal studies have shown that an IE > or = 0.07 is associated with rejection. Two of four patients with biopsy grade 0 or 1A rejection had no excess accumulation of labeled lymphocytes. The other two patients with biopsy grade 0 or 1A had an average IE of 0.13 +/- 0.04 (SD), which may actually represent the higher sensitivity of the scintigraphic approach, since the whole myocardium is interrograted. All four patients with biopsy grade 1B rejection had increased accumulation of labeled lymphocytes (IE = 0.18 +/- 0.06, P = .06 compared with all patients with grade 0 or 1A biopsies). CONCLUSIONS: The development of a sensitive, specific, and noninvasive method of diagnosing cardiac allograft rejection in humans might obviate the need for endomyocardial biopsy as well as improve the accuracy of diagnosis. The results suggest that scintigraphic detection of labeled lymphocytes is a promising approach for the noninvasive detection of cardiac transplant rejection. In addition, the approach should permit the assessment of the efficacy of antirejection therapy.

Imaging of thrombi with tissue-type plasminogen activator rendered enzymatically inactive and conjugated to a residualizing label.

BACKGROUND: Contemporary cardiovascular practice relies increasingly on thrombolysis as a therapeutic modality. Its optimal use requires prompt, noninvasive delineation of thrombotic occlusion in arterial beds and rapid detection of reocclusion after initially successful thrombolysis. METHODS AND RESULTS: We have been developing an approach to noninvasively image thrombi in which plasminogen-activating properties of tissue-type plasminogen activator (t-PA) are attenuated by treatment with D-Phe-L-Pro-L-Arg-chloromethyl ketone (PPACK) and have shown that the inactive t-PA avidly and promptly binds to clots in vitro. In the present study, we conjugated this material to a residualizing label, radioiodinated dilactitol tyramine (*I-DLT), and characterized the potential use of the inactivated, conjugated t-PA as a radiopharmaceutical for imaging thrombi in vivo. The approach developed requires not only avid binding of the tracer to thrombi but also rapid clearance from plasma and a lack of prompt release of radiolabeled degradation products from the liver. The rapid clearance of unaltered or PPACK-treated t-PA was not influenced by conjugation to *I-DLT, but the release of radioiodinated degradation products into plasma after injection of *I-DLT-conjugated t-PA was markedly less than release of degradation products of directly radioiodinated t-PA. When 131I-DLT-PPACK-t-PA was infused for 15 minutes intravenously after a bolus injection of 20% in dogs with coronary, pulmonary, or carotid artery thrombi, clearance was rapid. Mean +/- SEM thrombus-to-blood ratios of radioactivity were high, ranging from 37 +/- 9:1 and 2.8 +/- 0.6:1 with carotid thrombi formed concomitantly or approximately 30 minutes before infusion of tracer, respectively, to 35:1 for concomitantly formed coronary thrombi, 42 +/- 7:1 and 8.1 +/- 0.8:1 for concomitantly formed and preformed pulmonary thrombi, respectively, and 18:1 for a preformed femoral artery thrombus. Thrombi were detectable by planar gamma scintigraphy even though image quality was affected adversely by low concentrations of radioactivity that in aggregate composed a relatively large amount of radioactivity in underlying and overlying tissues. This limitation was overcome by tomographic imaging, which was used to detect both femoral and pulmonary thrombi. CONCLUSIONS: Use of enzymatically inactivated t-PA coupled to a residualizing label permits rapid detection and localization of thrombi in vivo.

Cloning and characterization of the HpaII methylase gene.

The HpaII restriction-modification system from Haemophilus parainfluenzae recognizes the DNA sequence CCGG. The gene for the HpaII methylase has been cloned into E. coli and its nucleotide sequence has been determined. The DNA of the clones is fully protected against cleavage by the HpaII restriction enzyme in vitro, indicating that the methylase gene is active in E. coli. The clones were isolated in an McrA-strain of E. coli; attempts to isolate them in an McrA+ strain were unsuccessful. The clones do not express detectable HpaII restriction endonuclease activity, suggesting that either the endonuclease gene is not expressed well in E. coli, or that it is not present in its entirety in any of the clones that we have isolated. The derived amino acid sequence of the HpaII methylase shows overall similarity to other cytosine methylases. It bears a particularly close resemblance to the sequences of the HhaI, BsuFI and MspI methylases. When compared with three other methylases that recognize CCGG, the variable region of the HpaII methylase, which is believed to be responsible for sequence specific recognition, shows some similarity to the corresponding regions of the BsuFI and MspI methylases, but is rather dissimilar to that of the SPR methylase.