MR monitoring of MR-guided radiofrequency thermal ablation of normal liver in an animal model

The purpose of this study was to determine the suitability of MRI to accurately detect radiofrequency (RF) thermoablative lesions created under MR guidance. In vivo RF lesions were created in the livers of six New Zealand White rabbits using a 2-mm-diameter titanium alloy RF electrode with a 20-mm exposed tip and a 50-W RF generator. This was performed using a 0.2T clinical C-arm MR imager for guidance and monitoring. Each animal was sacrificed and gross evaluation was performed. Histologic correlation was performed on the first two animals. The MR-compatible RF electrode was easily identified on rapid gradient-echo images used to guide electrode placement. A single lesion was created in each rabbit liver. Lesions ranged from approximately 10 to 17 mm in diameter (mean, 13.5 mm). T2-weighted and short T1 inversion recovery (STIR) images demonstrated lesions ranging in diameter from 12 to 18 mm (mean, 14.6 mm). Lesion dimensions determined from images closely correlated with those determined at gross examination with the discrepancy never exceeding 2 mm, for an r² value of .87. MRI performed at the time of MR-guided RF ablation accurately demonstrated created lesions. This modality may provide a new option for the treatment of local and regional neoplastic disease.     

Neurologic complications of reoperative and emergent abdominal aortic reconstruction

Patients undergoing emergent and reoperative abdominal aortic reconstructions are at increased risk for ischemic neurologic complications. Between 1986 and 1992 five patients sustained ischemic injuries to the spinal cord, nerve roots, or lumbosacral plexus. Four patients underwent reoperative aortic procedures including removal of an infected aortobifemoral graft and extra-anatomic bypass (n=3) and aortofemoral graft revision for primary graft failure (n=1). A fifth patient had a ruptured common iliac aneurysm repaired with an aortobifemoral graft. Three patients undergoing reoperative aortic procedures developed lower extremity paraparesis, patchy sensory deficits, and bowel and bladder dysfunction. Physical examination and electromyography localized the injury to the level of the cauda equina or lumbosacral plexus. The other patient in this group developed incomplete T12 paraplegia. Surgical reconstruction resulted in internal iliac exclusion in all four patients. The incidence of neurologic deficits during this study period was 18% (3/17) in patients requiring aortofemoral graft excision for infection. The patient undergoing aneurysm repair was noted to have paraplegia after surgery and died on the fourth postoperative day. Autopsy revealed evidence of multiple emboli to the kidneys, bowel, and spinal cord. Neurologic deficits after reoperative and emergent abdominal aortic reconstructions are uncommon but devastating complications. Of particular concern is the incidence of neurologic deficits after removal of aortofemoral grafts with disruption of collateral flow to the spinal cord and nerve roots. Consideration should be given to maintaining retrograde perfusion of at least one internal iliac artery via common femoral artery reconstruction in these patients.Presented at the Nineteenth Annual Meeting of the Peripheral Vascular Surgery Society, Seattle, Wash., June 5, 1994.     

The Ethics of Caring for Conjoined Twins The Lakeberg Twins

In June 1993, conjoined twins Amy and Angela Lakeberg became the focus of national attention. They shared a complex six-chambered heart and one liver; only one could survive separation surgery, and even her chances were slim. The medical challenge was great and the ethical challenges were even greater.     

Convulsive Therapy in the Treatment of Mania: McLean Hospital 1973-1986

The authors completed a retrospective chart review of the records of all patients identified with diagnoses of mania and schizoaffective disorder, manic type, who underwent electroconvulsive therapy between the years 1973 and 1986 at McLean Hospital. Ten of 18 manic patients (56%) and 3 of 9 schizoaffective patients (33%) experienced meaningful clinical benefit. The authors report the correlation of treatment and patient factors with outcome and review the literature on the convulsive therapy of mania.     

Importance of limbal examination in ocular allergic disease

We present three adult patients having classic symptoms of ocular allergy with findings confined to the limbus in all eyes. Findings in the cornea and the rest of the bulbar and tarsal conjunctivae were within normal limits. Case 1 had numerous limbal follicles; Case 2 had limbal chemosis 360 degrees; and Case 3 had superior perilimbal conjunctival injection, chemosis, and micropannus formation. Limbal scrapings from all patients revealed abundant eosinophils. There was marked clinical improvement after topical cromolyn sodium 4% treatment. Since the limbus was the only structure involved, the diagnosis of "allergic limbitis" was made. We feel that the limbus is an overlooked structure during ocular examination. As in our three cases, the limbus may be the only area involved in ocular allergy. A careful examination of the limbus may provide important clues for the diagnosis of many ocular inflammatory conditions.     

Synergistic antiviral activity of human interferon combinations in the hepatitis C virus replicon system.

The use of type I interferon (IFN), in combination with ribvirin, to treat chronic hepatitis C virus (HCV) infection has many drawbacks that prevent widespread application, ultimately leading to a significant unmet clinical need. Potential improvements in IFN therapy through targeted delivery, molecular alteration, and combination with other agents are ongoing in an attempt to decrease adverse effects and increase efficacy. In this report, the HCV replicon cell culture system was used to assess potential synergistic antiviral effects of multiple IFN species when administered in combination. Quantitative analysis of HCV replicon RNA by TaqMan (PE Applied Biosystems, Foster City, CA) and qualitative analysis of HCV protein expression were used to measure the antiviral efficacy of individual and combination IFN treatments, and synergistic responses of IFN combinations were determined through statistical analysis of the TaqMan results. We found that when administered simultaneously, type I/II IFN combinations (IFN-alpha2b + IFN-gamma or IFN-beta + IFN-gamma) resulted in dramatic antiviral synergy, whereas a type I/I combination (IFN-alpha2b + IFN-beta) demonstrated a slightly antagonistic profile. The synergistic effect is likely due to differential cell surface receptors and signaling pathways employed by types I and II IFNs. Conversely, all type I IFN species bind the same receptor and signal through similar pathways, possibly accounting for the nearly additive response observed. In support of this hypothesis, IFN treatment resulted in differential induction of Stat1 phosphorylation at Tyr 701. In conclusion, simultaneous type I/II IFN combination treatment may allow an overall decreased effective IFN dose, which may reduce the side effect profiles that hinder current therapy.     

Antibody-dependent cellular cytotoxicity (ADCC)-mediated destruction of human immunodeficiency virus (HIV)-coated CD4+ T lymphocytes by acquired immunodeficiency syndrome (AIDS) effector cells

The acquired immunodeficiency syndrome (AIDS) is defined in clinical terms by the development of Kaposi's sarcoma and/or severe opportunistic infections in persons without predisposing conditions. A hallmark of the syndrome has been a decrease in the number of CD4⁺ T helper cells. The reduction in the frequency of the CD4⁺ lymphocytes has been postulated to be primarily the result of human immunodeficiency virus (HIV) tropism and cytophathogenicity for the T-cell subset. Yet only a small percentage of cells is actually infected with HIV. Recently, we provided evidence indicating that AIDS patients' natural killer cells can mediate normal levels of antibody-dependent cellular cytotoxicity (ADCC) despite exhibiting a defect in natural killer (NK) effector function (J Immunol 139:55, 1987). This finding prompted us to investigate whether AIDS patients' effector cells could mediate ADCC against circulating CD4⁺ T cells infected with or expressing HIV antigen. The findings reported herein demonstrate that AIDS effector cells can mediate lysis of CEM (CD4⁺ T-cell line) coated with HIV protein in the presence of HIV-specific antibody. Lysis was specific, as non-HIV-coated CEM or the addition of HIV-negative serum resulted in no lysis. We then examined HIV-coated peripheral blood-derived CD4⁺ T lymphocytes as targets in ADCC. We demonstrate that in the presence of HIV-specific antibody, HIV-coated CD4⁺ T lymphocytes serve as targets for ADCC by AIDS effector cells. The lytic activity obtained with AIDS effector cells was comparable to that obtained with normal effector cells. These results demonstrate that AIDS effector cells can mediate ADCC against HIV-coated CD4⁺ T lymphocytes and suggest that ADCC may play a rolein vivo in the pathogenesis of AIDS.