Immunotoxin combined with chemotherapy for patients with AIDS-related non-Hodgkin's lymphoma

BACKGROUND: The objective of this study was to develop and test a combined therapeutic approach for patients with AIDS-related lymphoma (ARL), employing agents with independent mechanisms of action and nonoverlapping toxicity. This study was designed to test the feasibility and tolerance of combining low dose chemotherapy with infusional immunotoxin in the treatment of ARL patients. METHODS: Previously untreated patients received low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, and vincristine (m-BACOD) on a 21- to 28-day schedule. Patients who did not have progressive disease by Cycle 3 received anti-B4-blocked ricin (anti-B4bR), a murine monoclonal antibody linked to modified ricin, 20 microg/kg/day for 7 days administered by continuous infusion on an outpatient basis. A repeat cycle of anti-B4-bR was administered during Cycle 4 of chemotherapy based on tolerance. Patients received two cycles of chemotherapy beyond complete remission up to eight cycles. Study endpoints were toxicity, development of human antimurine antibody (HAMA) and human antiricin (HARA), tumor response, and survival. RESULTS: Twenty-six of 44 patients received the immunotoxin therapy. Anti-B4-bR infusion was associated with transaminase elevation (Grade 3) in 14 of 26 patients (58%), and flulike symptoms were common. HAMA or HARA was observed in 8 patients (31%). The overall response rate was 57% (13 complete responses and 12 partial responses). The median survival for all patients was 8.9 months. CONCLUSIONS: This study demonstrates the safety and feasibility of using chemotherapy and immunotoxin therapies in combination and supports their further evaluation to improve the outcomes of patients with ARL.     

Transient respiratory augmentation elicited by acute head-down tilt in the anesthetized cat

Acute head-down tilt (AHDT, -30 degrees) in humans induces a transient ventilatory augmentation for 1-2 min accompanied by a high venous return. However, the mechanisms underlying this respiratory response remain obscure because of limitations of experiments carried out in human subjects. The present study was undertaken to determine whether AHDT-induced respiratory augmentation exists in the anesthetized, paralyzed, and ventilated cat and, if so, whether this response depends on 1) the cerebellum, 2) the carotid sinus (CS) and/or vagal afferents, and 3) elevation of central venous return. The integrated phrenic neurogram, arterial blood pressure, central venous pressure (CVP), and end-tidal PCO2 were recorded before, during, and after AHDT. The results showed that AHDT produced a transient ( approximately 2 min) enhancement of minute phrenic activity (approximately 30%) primarily via an increase in peak integrated phrenic neurogram amplitude associated with a remarkable elevation of CVP (approximately 3 min). Cerebellectomy, CS denervation, bilateral vagotomy, or clamping CVP did not affect the presence of the AHDT-induced minute phrenic activity response. These findings demonstrate that the anesthetized cat is a suitable model for investigating the mechanisms involved in AHDT-induced respiratory augmentation. Preliminary studies suggest that this response does not require the cerebellum, CS/vagal afferents, or an associated rise in central venous return.     

An Adjustable Gain-Clamped Semiconductor Optical Amplifier (AGC-SOA)

The operation of a semiconductor optical amplifier (SOA)-ring laser-based subsystem, with the capability to provide adjustable gain-clamped operation, will be described, and preliminary characterization results will be presented. The device uses two SOAs in a ring-cavity topology: one to amplify the signal and the other to control the gain. This type of subsystem finds applications in packet-based dynamic systems where it may be used for power equalization and linear amplification.     

Educational issues in childhood cancer.

Discusses the general educational issues for children with cancer, with reference to the short- and long-term consequences of its type and treatment, and focuses on related assessment and intervention issues. Cognitive outcome and school performance are affected by the type and location of the tumor. Radiation therapy results in several side effects, like persistent vomiting and prolonged weight loss, which may interfere with ability to attend school, or cause long-term learning problems. Some chemotherapeutic agents may lower blood counts and affect the energy and concentration levels, or result in long-term neurodevelopmental problems. Deficits in processing speed, visual-motor integration attention and concentration may also result, especially in those under age 3–4 yrs. There must be repeated assessments and individualized educational plans based on understanding of school related effects in children with cancer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reversible amnesia associated with a left temporal hematoma in a case of right temporal complex partial seizures

We report the case of a 44-year-old woman with complex partial seizures (CPS) of right frontotemporal origin who developed generalized amnesia after undergoing intracranial electrode implantation complicated by left hippocampal hemorrhage. Serial memory testing disclosed recovery from the amnesic disorder, while repeated magnetic resonance imaging (MRI) showed resolution of her left hippocampal hemorrhage in a 2-month period. A second intracarotid amytal procedure confirmed the capability of her left temporal region to support memory. Consequently, a right orbitofrontotemporal lobectomy was performed without complication.     

Fosfomycin resistance protein (FosA) is a manganese metalloglutathione transferase related to glyoxalase I and the extradiol dioxygenases

The enzyme conferring resistance to the antibiotic fosfomycin [(1R,2S)-1,2-epoxypropylphosphonic acid] originally reported by Suarez and co-workers [Area, P., Hardisson, C., & Suarez, J. E. (1990) Antimicrob. Agents Chemother. 34, 844-848] is demonstrated in this study to be a metalloglutathione transferase. The apoenzyme is a dimer of 16 kDa subunits. Electron paramagnetic resonance spectroscopy and water proton nuclear magnetic resonance longitudinal relaxation rates suggest that each subunit contains a mononuclear Mn2+ center that interacts strongly with the substrate fosfomycin (Kd = 17 microM) more weakly with the product (Kd = 1.1 mM) and very weakly or not at all with GSH. Inhomogeneous broadening of the EPR signals of enzyme-bound Mn2+ in the presence of H2(17)O indicates that three of the coordination sites on the metal are occupied by water. Sequence alignments, three-dimensional structures, and mechanistic considerations suggest that FosA is related to at least two other metalloenzymes, glyoxalase I and the Mn2+- or Fe2+-containing extradiol dioxygenases. The mechanistic imperative driving the evolution of this previously unidentified superfamily of metalloenzymes is proposed to be bidentate coordination of a substrate or intermediate to the metal center in the enzyme-catalyzed reactions.     

Monkey cutaneous SAI and RA responses to raised and depressed scanned patterns: effects of width, height, orientation, and a raised surround

Monkey cutaneous SAI and RA responses to raised and depressed scanned patterns: effects of width, height, orientation, and a raised surround. J. Neurophysiol. 78: 2503-2517, 1997. The aim of this study was to examine the slowly adapting type I (SAI) and rapidly adapting (RA) primary afferent representation of raised and depressed surface features. Isolated, raised, and depressed squares and small raised squares with a circular surround were scanned across the receptive fields of SAI and RA mechanoreceptive afferents innervating the distal fingerpads of the rhesus monkey. Pattern height ranged from -620 to +620 micron and width ranged from 0.2 to 7.0 mm. The surround radii ranged from 3.0 to 7.0 mm. Previous combined psychophysical and neurophysiological studies have provided evidence that SAI afferent responses are responsible for the perception of spatial form and texture and that RA afferents are responsible for the detection of stimuli that produce minute skin motion (flutter, slip, microgeometric surface features). Our results strengthen these hypotheses. Response properties shared by both SAI and RA afferent types were that both responded only to the edges of the larger raised and depressed patterns, both responded to falling edges half as vigorously as to rising edges, both responded to rising and falling edges with impulse rates that were proportional to the sine of the angle between the edge and the scanning direction, and both had suppressed responses to a small raised surface feature when a raised surround was closer than 6 mm. Response differences consistent with the hypothesis that SAI afferents are specialized for the representation of form were that SAI responses were confined to areas around the features that evoked them in areas that were 40-50% smaller than the comparable RA response areas, SAI responses were more than four times more sensitive to stimulus height than were RA afferents over the range from 280 to 620 micron, and SAI (but not RA) afferents responded 20-50% more vigorously to corners than to edges. Response differences consistent with the hypothesis that RA afferents are specialized for the detection of minute surfaces features were that only RA afferents responded to very small surface depressions, depressed squares 0.8 mm wide, that were detectable by palpation. Mechanisms underlying the many differences in SAI and RA response properties are discussed.     

Performance of a wideband, three-stage, mixed geometry gyrotwystronamplifier

A three-stage, mixed geometry gyrotwystron amplifier has recently been operated and characterized at 4.5 GHz. Gyrotwystrons are hybrids of the gyroklystron and gyro-traveling-wave tube (gyro-TWT) amplifiers. In the device which was studied, the first two stages were tunable rectangular resonator cavities, and the third (output) stage was a circular cylindrical waveguide traveling wave section. All three stages operate in fundamental mode, and are separated by cut-off drift regions. This experiment was conceived as an extension of a previous three-cavity gyroklystron experiment, the motivation being to improve upon the gyroklystron instantaneous bandwidth of 0.4% while not sacrificing efficiency or gain. Measurements of gyrotwystron performance showed a 1.5% instantaneous bandwidth, a fourfold increase over that of the gyroklystron. The gain-bandwidth product of the gyrotwystron exceeded that of the gyroklystron by a factor of 6