Evaluation of soft-tissue masses using segmented color Doppler velocity images: preliminary observations

OBJECTIVE: We report our initial experience with segmented color Doppler velocity-based estimates of tumor vascularity for various histogically proven soft-tissue masses. SUBJECTS AND METHODS: Color Doppler sonography of 23 histologically proven masses in 22 patients was performed. Digital color Doppler images were acquired directly off the scanner output or from video recordings and stored on a personal computer as 24-bit gray-scale and color composite images. A color Doppler velocity segmentation and analysis algorithm was applied to the digital images, from which we calculated the normalized percentage of color Doppler area. Normalization was determined by expressing color Doppler area as a percentage of the area enclosed by a preselected region of interest. We also calculated mean percentage, SD, and cumulative distribution of color Doppler area, relative to a fixed threshold, for the acquired image data sets. RESULTS: Estimates of mean percentage of color Doppler area showed a dynamic range of at least two or three orders of magnitude between lowest and highest values obtained. A scatterplot of mean percentage of color Doppler area versus SD of percentage of color Doppler area showed a linear monotonic relationship (r2 = .92), illustrating increasing vascular heterogeneity with mean vascularity. Preliminary data also suggest the presence of at least two distinct groups of masses (p < .0001) based on these vascularity estimates. One group corresponds to high-grade lesions in which tumor angiogenesis is expected to be important in predicting biologic behavior. The second group appeared to have little or no relationship to tumor vascularity or was of an intermediate (or lower) histologic grade. CONCLUSION: Quantitative color Doppler estimates of tumor vascularity can be obtained over a wide dynamic range. Such estimates provide a mechanism to assess vascular heterogeneity of soft-tissue tumors. Preliminary data suggest that two biologically distinct groups of masses may be separable on the basis of quantitative velocity-based estimates of tumor vascularity as obtained from color Doppler sonography.     

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.     

A pilot study on the motor effects of rimantadine in Parkinson's disease

The purpose of this pilot study was to determine whether rimantadine, the alpha-methyl derivative of amantadine, might have any antiparkinsonian properties. In an open-label trial, 14 patients (12 de novo and 2 on levodopa treatment) with Hoehn and Yahr stage 2 to 3 Parkinson's disease were placed on rimantadine at doses of 100 to 300 mg/d. No patients had dyskinesias or motor fluctuations. Ten of 14 (71%) reported a mean subjective response of 33% (range 10%-60%) to rimantadine. After treatment, there was a 13% improvement in Hoehn and Yahr staging (p = .01) and a 20% improvement in mean motor Unified Parkinsons Disease Rating Scale scores (p = .02). Rigidity was the most consistently improved feature among the responders. Mean effective dose was 256 mg/d (range 200-300 mg/d). Side effects were mild and transient, with nausea being most common (4/14). We conclude that rimantadine has some motor benefits in Parkinson's disease. A double-blind placebo-controlled study is warranted to validate our findings.     

Mechanism of action of sodium cyanide on rat diaphragm muscle.

The effects of sodium cyanide (NaCN) were investigated on the contractile and electrophysiological properties of rat diaphragm muscles in vitro. Sodium cyanide (0.1-1.0 mM) produced an initial potentiation of directly elicited twitch tensions, followed by a slow progressive depression. The potentiation and depression were both dependent on the NaCN concentration and stimulation frequency. Muscles exposed to NaCN exhibited marked reductions of creatine phosphate concentration, but ATP levels were not significantly lowered. Sodium cyanide had no effect on the resting potential, input resistance or action potential, indicating that the toxicity of the metabolic inhibitor is not mediated by alterations of membrane excitability or passive electrical properties. Sodium cyanide reduced the amplitude of contractures elicited by 70 mM K(2)SO(4), suggesting that the actions of NaCN cannot be explained by a failure of action potentials to propagate across the muscle surface or within t-tubular membranes. Sodium cyanide suppressed the first phase of the caffeine contracture, an observation consistent with an impaired release of, or reduced sensitivity to, sarcoplasmic reticular Ca(2+), but did not alter the amplitude of the second phase, which represents rigor following ATP depletion. These results, in conjunction with those of previous studies, suggest that the depression in muscle tension following exposure to NaCN may result from alterations in Ca(2+) homeostasis, intracellular acidosis or from accumulation of one or more products of phosphocreatine breakdown.     

Evaluation of phosphoramidon and three synthetic phosphonates for inhibition of botulinum neurotoxin B catalytic activity

Three putative metalloprotease inhibitors were synthesized and tested for their ability to inhibit the catalytic activity of botulinum neurotoxin B light chain (BoNT/B LC). The compounds were designed to emulate the naturally occurring metalloprotease inhibitor phosphoramidon, which has been reported to be a weak antagonist of BoNT/B action. All three analogs contained the dipeptide Phe-Glu in place of Leu-Trp of phosphoramidon and possessed a phenyl, ethyl or methyl group in place of the rhamnose sugar of the parent compound. The inhibitors were evaluated in a cell-free assay based on the detection of a fluorescent product following cleavage of a 50-mer synaptobrevin peptide ([Pya(88)] S 39-88) by BoNT/B LC. This peptide corresponds to the hydrophilic core of synaptobrevin-2 and contains a fluorescent analog L-pyrenylalanine (Pya) in place of Tyr(88). Cleavage of [Pya(88)] S 39-88 by BoNT/B LC gives rise to fragments of 38 and 12 amino acid residues. Quantification of BoNT/B-mediated substrate cleavage was achieved by separating the 12-mer fragment (FETSAAKLKRK-Pya) that contains the C-terminal fluorophore and measuring fluorescence at 377 nm. The results indicate that the phenyl-substituted synthetic compound ICD 2821 was slightly more active than phosphoramidon, but analogs with methyl or ethyl substitutions were relatively inactive. These findings suggest that phosphonate monoesters may be useful for providing insights into the structural requirement of BoNT/B protease inhibitors.     

Limb preservation for reimplantation. a review

Although reimplantation of severed limbs and other parts of the body has become prevalent in recent years, the questions of how best to preserve limbs for reimplantation and how to determine if a transected part is viable have not been fully answered. The problem of preservation involves combating direct anoxic damage to tissue as well as combating the changes in the vascular system that lead to the "no reflow phenomenon." Current information concerning kidney preservation as well as experimental and clinical reports on limb preservation are reviewed in this article, and suggestions are made for further investigations.     

Patient-based health status assessments in an outpatient psychiatry setting

OBJECTIVE: The reliability, validity, and feasibility of the routine use of a generic health status instrument, the Short-Form-36 Health Survey (SF-36), were examined in a psychiatric outpatient clinic of a general hospital. METHODS: The sample comprised 411 patients referred to an outpatient psychiatry department between April 1994 and March 1995. They filled out the SF-36 along with their admission forms. Scores and reports were generated, and the results were returned to the charts and used at weekly clinical conference discussions. Feasibility was evaluated using subjective and objective data on administration of the instrument, its psychometric properties, and costs. Results from the outpatient psychiatry patients were compared with those from patients scheduled for elective surgery and a healthy normative sample. RESULTS: Routine administration of the SF-36 was successfully achieved with minimal resistance from staff and patients. The SF-36 provided reliable and valid data. As predicted, patients with emotional disorders scored lower, indicating more impairment, on scales measuring mental health than did the elective surgery patients and the normative sample. However, the psychiatric patients' scores on the physical health scale were lower than clinicians expected. Compared with the elective surgery patients, the psychiatric patients were less impaired on only the physical functioning and bodily pain scales; no difference was found between the two groups in role functioning due to physical problems. CONCLUSIONS: Routine use of the SF-36 in a general hospital psychiatric outpatient clinic was feasible, and the results were reliable, valid, and helpful to clinicians. Psychiatric patients' significantly lower scores in physical health and social and role functioning provided additional information about their difficulties.