Brief communication: Hexamethylmelamine in adenocarcinoma of the pancreas and liver

Ten patients with advanced adenocarcinoma of the pancreas were treated with hexamethylmelamine 8 mg/kg/day in oral, divided doses. One of the five patients with measurable disease had a partial response which lasted 5 months. One of the five patients with no measurable disease treated for 52 months with hexamethylmelamine survived a total of 59 months. This experience suggests that hexamethylmelamine may be an active drug in the treatment of pancreatic cancer.     

Behavioral training increases local astrocytic metabolic activity but does not alter outcome of mild transient ischemia

Functional neurological outcome after transient ischemia might be improved by timely therapeutic intervention. To determine if restorative behavioral therapy influences damage, improves task learning, or alters astrocyte metabolic activity after ischemia, rats (food-restricted to 85% of free-feeding weight) were (a) first trained to respond on one of two levers under a fixed-ratio 20 schedule of food presentation (FR20), then (b) subjected to sham manipulation of carotid arteries or 10 min ischemia by four-vessel occlusion, followed by (c) 4 days of operant testing or inactivity, (d) then all rats were tested under a FR20 lever reversal task for 4 weeks, and (e) 3 days after the last behavioral session astrocyte metabolism was assayed by local uptake of [2-14C]acetate. Mild loss of hippocampal neurons occurred in ischemic rats with or without training after ischemia. Glial fibrillary acidic protein-positive astrocytes were present in similar numbers throughout brains of sham control and ischemic rats. Mild ischemia did not impair learning, and no changes in FR20 reversal learning were detected in sham vs. ischemic rats. Net [14C]acetate uptake was unaffected by ischemia but [14C]acetate uptake increased 15-24% (P<0.05; n=12-15/group) in specific structures (caudate, primary motor and sensorimotor cortex, CA1 hippocampus, subcortical white matter) in the pooled groups of rats that had 4 days FR20 testing vs. inactivity before reversal learning. 'Behavioral therapy' (operant testing on the 4 days immediately following either sham manipulation or ischemia) did not alter ischemic outcome, but was associated with higher acetate utilization in regions involved in motor activities.     

Forearm EMG response activity during motor performance in individuals prone to increased stress reactivity

BACKGROUND: Work-related Upper Extremity Disorders (WRUEDs) are conceived of as a multifactorial syndrome caused by the effects of excessive repetitive motions, sustained static postures, and muscular stiffness. Our aim is to test an etiological model derived from a theory by Van Galen and Van Huygevoort [2000] Biol Psychol 51:151-171. The theory holds that physical, emotional, and psychosocial stressors enhance muscular stiffness as a compensatory filtering of impoverished signal-to-noise ratios in the motor system. High individual levels of arousal, as measured by Spielberger et al. [1970], State and Trait Anxiety Test would further enhance a subject's predisposition to react with stiffness responses in conditions of stress. METHODS: Ten participants with a high- and 10 with a low trait-anxiety score performed a computer task involving series of fast but well-dosed accelerations of the forearm along the surface of a digitizer. To induce cognitive stress a tone had to be remembered simultaneously with the aiming task. Pen-tip displacements and surface electromyographic (EMG) signals were recorded from four forearm muscles. RESULTS: Memory load did not affect error rates but produced shorter reaction times and prolonged movement times. EMG data show that under stress overall levels of neuromotor activation were enhanced. High-anxious participants exhibited higher cocontraction levels than low-anxious participants. CONCLUSIONS: The findings support the view that stress and muscular tension are closely related and may provide a clue to the origin of WRUEDs.     

Video-oculography in the gerbil

Normative vestibulo-ocular and optokinetic reflexes (VOR and OKR) and pupil diameter were measured in young adult gerbils using infrared video-oculography with 60 Hz sampling during head-fixed binocular recordings. The pupillary light-sink technique was preferred over a single-beam retinal reflection method because its measurements were less affected by pupil size. Eye movements were generally conjugate with occasional independent saccadic movements, and independent drifting movements in the dark. The horizontal optokinetic response to sinusoidal motion of a randomly spaced white dot pattern was maximal at low velocities (5 degrees/s), stronger temporonasally, and dropped off quickly at approximately 20 degrees/s. Constant velocity gain was near unity through 60-80 degrees/s with a sharp drop-off. Monocular viewing revealed almost no nasotemporal optokinetic response. Pupil diameter was found to vary as a saddle function with optokinetic gain from cycle to cycle, but also have a circadian rhythm (smaller at dusk) that related inversely to mean horizontal VOR gain. Gerbils with eyes open sometimes had no optokinetic response during long stimulus periods, which then resumed after a brief vestibular stimulus. The horizontal angular VOR gain was relatively flat across 0.1-1.0 Hz and 30-120 d/s sines (phase near zero), with a mean gain of approximately 0.78 in the dark, and 1.0 with the fixed pattern surround (n=15, for both raw calibrated and normalized data). Most animals also revealed a strong slow phase eye velocity asymmetry (dominant during ipsilateral rotation) in the half-cycle gain of their horizontal angular VOR response in the dark. A constant velocity horizontal optokinetic bias velocity did not change the gain or symmetry of the sinusoidal VOR response, but shifted the VOR response velocity in an additive (linear) fashion. Both cross-coupling (pitch or roll while rotating) and pseudo-OVAR (off-axis counter-rotation) stimuli generated horizontal nystagmus. The findings suggest that the gerbil, like other lateral-eyed rodents, relies on otolith cues to interpret angular motion.     

The suitability of cells from different tissues for use in tissue-engineered skin substitutes

Tissue-engineered skin substitutes may be a future remedy for burn wounds and chronic wounds, as wound contraction and scar formation cannot be prevented with the current standard treatment. The aim of this study therefore was to identify readily available sources of fibroblasts suitable for dermal substitution. Three different tissues were studied: dermal tissue from split-skin graft, subcutaneous fat tissue and eschar tissue obtained through debridement of burn wounds. We determined the cellular profile and the cell numbers immediately after isolation and after 2 and 14 days of fibroblast culture using flow cytometry and cell counting with a cytometer. In addition, parts of the isolated cell suspensions were seeded directly into a porous collagen dermal substitute to investigate contraction over time. Various cell types were isolated from the three different tissues, but after 14 days of culturing predominantly fibroblasts (>90%) were detected. Keratinocytes, granulocytes and macrophages, if present, disappeared within 14 days. In the cell populations derived from dermal tissue, the percentage of myofibroblasts had decreased significantly by day 14 (from 8% to 3%, P=0.028). In contrast, this percentage had increased in the cell populations derived from fat and eschar (from 23% to 40% and from 20% to 38%, respectively). The fibroblast yield from dermal tissue after 2 weeks of culturing (50 x 10(6) cells/g of tissue) was significantly higher than the yield from fat and eschar tissue (2 x 10(6) cells/g of each tissue, P=0.029). Immunohistochemistry of collagen matrices seeded and cultured with fat- and eschar-derived cells revealed a high prevalence of myofibroblasts, whereas hardly any myofibroblasts were detected in the matrices seeded with dermal cells. The contraction of the eschar matrices was highest (74+/-6% remaining area), whereas dermal matrices contracted significantly less (92+/-7% remaining area, P=0.029) with intermediate contraction for fat matrices. We conclude that fibroblast cultures can be established from dermal tissue, fat tissue and eschar tissue. Dermis is the best fibroblast source for use in skin substitutes as it yields the highest numbers of fibroblasts with minimal numbers of myofibroblasts.     

Posterior distal femoral and proximal tibial metaphyseal stripes at MR imaging in children and young adults

PURPOSE: To determine the frequency and distribution of the hyperintense stripe seen along the posterior surface of distal femoral and proximal tibial metaphyses at magnetic resonance (MR) imaging. MATERIALS AND METHODS: One hundred forty-two MR imaging studies obtained in 139 children and young adults were reviewed. The authors recorded the presence and distribution of posterior distal femoral and proximal tibial metaphyseal stripes. Presence of stripe was correlated with patient age and sex and with patency of the adjacent physis. Fifty-nine studies of adults were reviewed similarly. Two-way analysis of variance was performed to compare mean patient age for sex among four different categories that were based on stripe presence and physeal patency. Orthogonal contrasts were used to determine whether a linear trend across the categories existed. In one cadaveric femur, imaging and histologic analysis were performed. RESULTS: A metaphyseal stripe was seen in all patients with a completely or partially open physis (110 femora, 102 tibiae) and in 56 femora and 60 tibiae in the patients with fused physes. Thirty-five femora and 35 tibiae showed no stripe; all patients were skeletally mature. Correlations between metaphyseal stripe visualization and physeal patency were significant (P <.001). Differences in mean patient age among the four categories were significant for both (femoral and tibial) locations (P <.001), and a linear trend with age (P <.001) was demonstrated. This linear trend was also observed in both sexes (P <.001). Histologic analysis revealed highly vascular loose fibrous tissue. CONCLUSION: A posterior metaphyseal stripe is seen at MR imaging of the skeletally immature knee and likely reflects normal bone growth.     

Transvenous embolization of a direct carotid cavernous fistula through the pterygoid plexus

Closure of a direct carotid cavernous fistula with detachable coils by transpterygoid venous approach to the cavernous sinus is an alternative technique that may be applied in cases in which other techniques offer increased risk or in which other techniques have failed. In this case report, we present the details of the management of a direct carotid cavernous fistula by this method.