T cell vaccination in multiple sclerosis: results of a preliminary study

Myelin basic protein (MBP)-reactive T cells are potentially involved in the pathogenesis of multiple sclerosis (MS), and can be depleted by subcutaneous inoculations with irradiated autologous MBP-reactive T cells (T cell vaccination). This preliminary open label study was undertaken to evaluate whether depletion of MBP-reactive T cells would be clinically beneficial to patients with MS. Fifty-four patients with relapsing-remitting (RR) MS (n=28) or secondary progressive (SP) MS (n=26) were immunized with irradiated autologous MBP-reactive T cells and monitored for changes in rate of relapse, expanded disability scale score (EDSS) and MRI lesion activity over a period of 24 months. Depletion of MBP-reactive T cells correlated with a reduction (40 %) in rate of relapse in RR-MS patients as compared with the pre-treatment rate in the same cohort. However, the reduction in EDSS was minimal in RR-MS patients while the EDSS was slightly increased in SP-MS patients over a period of 24 months. Serial semi-quantitative MRI examinations suggest stabilization in lesion activity as compared with baseline MRI. The findings suggest some potential clinical benefit of T cell vaccination in MS and encourage further investigations to evaluate the treatment efficacy of T cell vaccination in controlled trials. Received: 27 November 2000, Received in revised form: 10 May 2001, Accepted: 11 June 2001     

Neuroendocrine tumors of the pancreas in von Hippel-Lindau disease: spectrum of appearances at CT and MR imaging with histopathologic comparison

PURPOSE: To demonstrate the imaging characteristics of neuroendocrine tumors (NETs) of the pancreas in patients with von Hippel-Lindau (VHL) disease to establish diagnostic criteria. MATERIALS AND METHODS: Twenty-five patients with VHL disease and 29 surgically confirmed pancreatic NETs were included. Screening computed tomographic (CT) and/or magnetic resonance (MR) imaging findings were reviewed, and tumor number, diameter, growth rates (doubling time), location, presence of metastatic disease, and attenuation or enhancement properties were determined. RESULTS: Eighteen of 29 (62%) pancreatic NETs were smaller than 3.0 cm in diameter and enhanced homogeneously on contrast material-enhanced CT and MR images. No tumor smaller than 3.0 cm metastasized. Tumors 3.0 cm or larger (11 [38%] of 29) more often enhanced heterogeneously, and two of 11 were associated with hepatic metastases. Smaller (<3.0 cm) tumors displayed longer mean doubling times (mean, 927 vs 351 days) than did larger (> or =3.0 cm) tumors; however, there was considerable overlap. Fifteen (52%) tumors were located in the pancreatic head; eight (28%), in the tail; and six (21%), in the body. Ten (40%) patients with pancreatic NETs had associated pheochromocytomas, and 22 (88%) had no or mild pancreatic cystic disease, which is substantially more than the general population of patients with VHL disease. CONCLUSION: Pancreatic NETs in VHL have characteristic features at CT and MR imaging: Most are small, located in the pancreatic head, and enhance homogeneously. Tumors larger than 3.0 cm are prone to metastasize and enhance heterogeneously.     

Mid-Systolic closure of the aortic valve in hypertrophic obstructive cardiomyopathy: A pressure-Related phenomenon induced by turbulent blood flow

The purpose of this study was to determine whether mid-systolic closure and opening of the aortic valve in patients with hypertrophic obstructive cardiomyopathy (HOCM) may reflect dynamic changes of pressure induced by turbulent blood flow in the aorta and left ventricular outflow tract. Five patients with HOCM who had echocardiographic evidence of mid-systolic closure of the aortic valve and two patients with HOCM who did not have transient mid-systolic closure of the aortic valve were studied. In patients in whom mid-systolic closure was present, a transient mid-systolic drop of pressure was present in the left ventricular outflow tract, distal to the dynamic intraventricular obstruction, 17 ± 3 mm Hg (mean ± SEM) and in the root of the aorta, 16 ± 4 mm Hg. In these patients the mid-systolic drop of pressure was consistently associated with a high-intensity intracardiac murmur indicative of turbulence. In the two patients in whom mid-systolic closure of the aortic valve was absent, the transient mid-systolic drop of pressure during systole was minimal (average, 3 mm Hg). The transient mid-systolic drop of pressure distal to the intraventricular obstruction can be explained on the basis of decreased pressure energy of the blood due to turbulence. Since total energy is conserved, increased kinetic energy due to turbulence occurs at the expense of a loss in pressure energy. The transient mid-systolic reduction of pressure in the turbulent zone during systole may cause a pressure differential across the open valvular leaflets resulting in a transient closure of the aortic valve.     

The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis

Callus distraction is currently the most popular method of bone lengthening. Prolonged treatment time is one of its major problems. In this study, we investigated the effect of low-intensity pulsed ultrasound on tibial distraction osteogenesis. We managed 20 patients with tibial defects ranging from 5 cm to 8 cm with distraction osteogenesis using the Ilizarov external fixator. After the completion of distraction, ten patients received daily 20 min of low-intensity pulsed ultrasound stimulation (30 mW/cm²) onto the bone lengthening site (group A) while rigid fixation was maintained in the remaining patients (group B). All patients were followed with weekly radiographs to determine the formation of an external cortex and an intramedullary canal, at which time the fixator was removed. The mean healing index in group A was 30 (27–36) days/cm while it was 48 (42–75) days/cm in group B. In group B, one patient failed to consolidate the regenerated bone. Low-intensity pulsed ultrasound stimulation is highly effective in achieving maturation of bone and reducing time of distraction osteogenesis.

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Résumé La distraction du cal est la méthode dallongement de los la plus populaire actuellement. La longueur du traitement est un de ses problèmes majeurs. Nous avons étudié leffet des ultrasons pulsés de basse intensité sur lostéogenèse dans la distraction tibiale.Nous avons traité 20 malades présentant un défaut tibial de 5 à 8 centimètres avec ostéogenèse de distraction utilisant un fixateur externe dIlizarov. Après lachèvement de la distraction 10 malades ont reçu quotidiennement une stimulation par ultrasons (30 mW/cm²) sur lemplacement de lallongement osseux pendant 20 minutes (groupe A), pendant que la fixation rigide était maintenue pour le restant des malades (groupe B). Tous les malades ont été suivis avec des radiographies hebdomadaires pour déterminer la formation dun cortex périphérique et dun canal intramédullaire au moment ou le fixateur a été enlevé. Lindex de consolidation moyen dans le groupe A était 30 (27–36) jours/cm pendant quil était 48 (42–75) jours/cm dans le groupe B. Dans le groupe B un malade na pas consolidé los régénéré. La stimulation par ultrasons pulsés de basse intensité est très efficace pour favoriser la maturation osseuse et réduire le temps dostéogenèse dans la distraction.

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None of the authors received financial support for this study.     

Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota

Context  Limited data exist regarding population-based epidemiologic changes in incidence of infective endocarditis (IE). Objective  To evaluate temporal trends in the incidence and clinical characteristics of IE. Design, Setting, and Patients  Population-based survey using the resources of the Rochester Epidemiology Project of Olmsted County, Minnesota. One hundred seven IE episodes occurred in 102 Olmsted County residents between 1970 and 2000. The modified Duke criteria were used to validate the diagnosis of definite or possible IE. Main Outcome Measures  Incidence of IE, proportion of patients with underlying heart disease, and causative microorganisms and clinical characteristics. Results  Age- and sex-adjusted incidence of IE ranged from 5.0 to 7.0 cases per 100 000 person-years during the study period and did not change significantly over time (P = .42 for trend). Infective endocarditis caused by viridans group streptococci was the most common organism-specific subgroup, with an annual adjusted incidence of 1.7 to 3.5 cases per 100 000; in comparison, IE due to Staphylococcus aureus had an annual adjusted incidence of 1.0 to 2.2 cases per 100 000. No time trend was detected for either pathogen group (P = .63 and P = .66, respectively). An increasing temporal trend was observed in the proportions of prosthetic valve IE cases (P = .09). Among people with underlying heart disease, there was an increasing temporal trend in mitral valve prolapse (P = .04) and a decreasing trend in rheumatic heart disease (P = .08). However, the absolute numbers were small. There was no time trend in rates of valve surgery or 6-month mortality during the study period (P = .97 and P = .59, respectively). Conclusions  In this community-based temporal trend study, we found no substantial change in the incidence of IE over the past 3 decades. Viridans group streptococci continue to outnumber S aureus as the most common causative organisms of IE in this population.