Detection of liver fibrosis with magnetic cross-relaxation

The utility of MRI using magnetization transfer (MT) enhanced pulse sequences to diagnose hepatic cirrhosis in a rat model was investigated. Hepatic T₁ was measured with and without MT off-resonance RF pulses in 17 treated and six control rats. The livers were evaluated histologically, and the hydroxyproline content quantitatively measured. We did not find a statistically significant linear correlation between the MR relaxation times and the degree of tissue injury. However, the MR measurements performed with MT were superior to those without differentiating the treated and control groups. Specifically, the T₁ times were 695 ±76 ms for the treated group, versus 748 ± 61 ms in the controls; P= 0.095. The T_1sat times were also lower in the treated group, with statistical significance: 367 ± 51 ms versus 421 ± 38 ms, P = 0.016. Finally, the change in the relaxation rates (the inverse of the relaxation times) with and without saturation were 1.31 ± 0.22 s^?1 (treated group) versus 1.05 ± 0.12 s^?1 (controls), which differed significantly, P= 0.001.     

Peripheral mechanical loading and the mechanism of the tremor of chronic alcoholism.

The tremor of chronic alcoholism, although clinically similar to essential tremor, has been considered a distinct syndrome. Its underlying mechanism was analyzed in five patients (none in the acute stages of alcohol withdrawal) hospitalized in an alcohol detoxification program. All five patients performed tracking tasks in which they pursued a linearly moving "target" light with a response light that they controlled by flexion-extension activity of the wrist. Stationary and dynamic targets were used with both isometric and unconstrained wrist mechanical interfaces. Frequency, torque, and displacement tremor characteristics were examined under varying inertial loading or isometric voluntary torque conditions. Two simultaneous tremor components were present in all patients: a prominent 4- to 7-Hz low-frequency peak and a smaller-amplitude 9.4- to 9.6-Hz high-frequency peak. As the inertia of the hand was augmented during unconstrained tasks, the low-frequency peak decreased, while the high-frequency peak was unaffected. As required voluntary effort was increased during isometric testing, the amplitude of the low-frequency peak increased. These findings suggest that the low-frequency peak represents the significant pathologic component of the tremor of chronic alcoholism and that it has a biomechanical reflex mechanism similar to that of the lower-amplitude normal physiologic tremor.     

Synthesis of melanin-like pigments by Sporothrix schenckii in vitro and during mammalian infection

Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen Sporothrix schenckii produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells. S. schenckii grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from S. schenckii yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with S. schenckii contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that S. schenckii conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis.     

Magnetic resonance imaging of femoral head development in roentgenographically normal patients

Magnetic resonance images (MRI) of 22 patients with roentgenographically normal hips were reviewed retrospectively and the findings categorized according to age. With increasing maturity, the MR intensity of the femoral heads on spin echo images increased, as marrow fat became a dominant tissue in the head. The femoral head pattern was relatively inhomogeneous, with a broad band of diminished intensity extending in a posteromedial to anterolateral direction, corresponding to the pattern of trabecular bone. The femoral capital epiphyses were visible in younger patients as structures of bright intensity which remained evident through early adulthood. The articular cartilage of the hip joint was noted as a distinctive halo around the femoral head. An understanding of the MR pattern of the normal hip will aid in the early recognition of pathologic conditions, such as osteonecrosis.     

Robot training enhanced motor outcome in patients with stroke maintained over 3 years

In an attempt to improve motor recovery of the upper limb after stroke, we added a robot (MIT-Manus) experience that provided additional goal-directed sensorimotor activity to standard rehabilitation treatments. The first trial produced a significant decrease in motor impairment in the upper limb for the treated group. In re-evaluating 12 of those 20 patients, nearly 3 years later, robot-trained patients showed further significant decreases in impairment measures of the affected limb. The groups were comparable at the start of the study.     

Considerations in the design of clinical trials for cognitive aging

What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging.     

Pulmonary Embolism Presenting as Fever in Spinal Cord Injury Patients: Report of Two Cases and Review of the Literature

ABSTRACT

Pulmonary embolism is a common, sometimes fatal complication of spinal cord injury. We describe two quadriplegic patients who developed unexplained fever as the sole presenting sign of multiple pulmonary emboli during the subacute phase following injury. These cases and a review of the literature suggest that ventilation-perfusion scanning should be considered in the diagnostic evaluation of fever in patients with recent spinal cord injury even in the absence of other clinical signs of thromboembolic disease.     

Distribution of iron between the binding sites of transferrin in serum: methods and results in normal human subjects.

When it is incompletely saturated with iron, transferrin may exist in four molecular forms: apotransferrin, monoferric (A) transferrin (with iron occupying only the A site of the protein), monoferric (B) transferrin, and diferric transferrin. By combining electrophoresis in urea-polyacrylamide gels with crossed immunoelectrophoresis using specific antihuman transferin antiserum, it is possible to display and estimate the concentration of each of these four forms in normal human serum. The distribution of iron between the binding sites of transferrin is neither random nor determined by the relative binding strengths of transferrin's two sites. Rather, the more weakly binding and acid-labile B site of the protein is predominantly occupied.