Velocity of peristaltic propagation in distal esophageal segments

Recent studies of the peristaltic pressure wave have suggested the presence of two sequential but overlapping contraction segments in the distal esophageal body. In this report, propagation velocity of esophageal peristalsis was determined in these segments in normal subjects (N=35) and in patients with high-amplitude peristalsis (nutcracker esophagus,N=25) to see if intersegment differences were present in the normal or abnormal setting. Velocity measurements were made from conventional manometric tracings in two 4-cm regions representing the distal smooth-muscle segments. A novel method of velocity measurement was employed that used regression lines established from contraction onset times. In normal subjects, propagation velocity decreased significantly from the proximal to distal segment (4.9±0.5 cm/sec, vs 3.2±0.2 cm/sec,P<0.01). Velocity also decreased across segments in nutcracker-esophagus patients (5.3±0.6 cm/sec, vs 3.6±0.7 cm/sec,P=0.06), but the difference reached statistical significance only when the subset with highest amplitudes (180 mm Hg) was analyzed separately. Greater variance in velocity in the distal smooth-muscle segment of nutcracker-esophagus patients (P<0.01) was, in part, responsible for this statistical observation. We conclude that normal propagation velocity decreases across regions corresponding to the smooth-muscle contraction segments defined by recent studies of peristalsis, supporting the assumption that they represent separate neuromuscular units. The mechanisms responsible for contraction wave abnormalities in the nutcracker esophagus have a minimal effect on propagation velocity, an effect that is restricted to the distal smooth-muscle segment of the esophageal body.Supported in part by a grant from the United States Public Health Service (AM07130).     

Corticomuscular coherence: a review.

Corticomuscular coherence measured between electroencephalography (EEG), magnetoencephalography, or local field potentials and electromyography (EMG) should be helpful in understanding the cortical control of movement. EEG-EMG coherence and phase spectra depend on the types of EEG derivation and current source density function of EEG appears to be the most appropriate for computation of EEG-EMG coherence. A new model for the interpretation of the phase spectra ("constant phase shift plus constant time lag model") shows that cortical surface negative potentials are phase-locked to EMG firing. There are functional differences of EEG-EMG coherence among the alpha, beta, and gamma bands suggesting differences in their possible generator mechanisms. Since corticomuscular coherence is a noninvasive measure of corticomotoneuronal function in a specific frequency range, clinical application of this method might be very fruitful in tremor research.     

Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.

Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections.     

Timing of activity in early visual cortex as revealed by transcranial magnetic stimulation

To determine the timing of visual processing in the early visual cortex, we applied single pulse transcranial magnetic stimulation to the occipital pole of healthy subjects while they were engaged in a forced-choice visual letter-identification task. We found two separate periods of activity, the first ranging from 20 to 60 ms after the onset of the visual stimulus, and the second ranging from 100 to 140 ms after the onset of the visual stimulus. We suggest that these two periods reflect necessary activity in V1, before and after re-entry.     

Gamma linolenic acid inhibits tyrosine phosphorylation of focal adhesion kinase and paxillin and tumour cell matrix interaction

Gamma linolenic acid (GLA) is an anti-cancer agent recently reported to inhibit tumour cell-matrix attachment. This study examined the effects of GLA on the adhesion of two tumour cell lines, HT115 (human colon) and MDA MB 231 (human breast), to an extracellular matrix, Matrigel. The action of GLA on focal adhesion kinase(FAK) and paxillin was also investigated. Following cell adhesion to Matrigel in control experiments, both FAK and paxillin were quickly tyrosine phosphorylated and become concentrated at focal adhesion areas. Inclusion of GLA resulted in an inhibition of the tyrosine phosphorylation of both FAK and paxillin leading to a reduced attachment of both cell types to Matrigel. FAK and paxillin were also less well distributed in the focal adhesions compared with the controls. It is concluded, therefore, that GLA inhibits tumour-matrix adhesion via the inhibition of FAK and paxillin tyrosine phosphorylation.     

Inhibition of membrane ruffling and ezrin translocation by gamma linolenic acid

Membrane ruffling of a tumour cell is correlated with its motile and metastatic behaviour. This study examined the effect of gamma linolenic acid (GLA), an anti-cancer agent, on HGF/SF induced membrane ruffling in the human cancer cell line, HT115. HGF induced a rapid appearance of membrane ruffling which was related to increased motility and the tyrosine phosphorylation and translocation of ezrin, a membrane-cytoskeleton linker protein. The presence of GLA significantly inhibited both the membrane ruffling and cell motility of the tumour cells, at sub-toxic concentrations. Western blotting revealed that the tyrosine phosphorylation of ezrin was inhibited by GLA. The translocation ezrin from cytosol and generalised areas of cell membrane to ruffled areas of the membrane induced by HGF/SF was also inhibited as shown by both indirect immunofluorescence and transmission electron microscopy. It is concluded that GLA inhibits HGF/SF induced membrane ruffling via its effect on ezrin, and this provides a further molecular explanation for the anti-tumour action of GLA.     

Totally laparoscopic aortobifemoral bypass grafting in an experimental model: Description of technique with initial surgical results

Our aim was to examine the feasibility of a totally laparoscopic insertion of a bifurcated aortofemoral bypass graft in a canine model and to compare the surgical results with those in control animals undergoing standard grafting and laparoscopic-assisted bypass procedures. Using a six-port approach, we exposed and cross clamped the aorta, tunneled a bifurcated Dacron graft, and performed an end-to-end aortic anastomosis while maintaining pneumoperitoneum by means of CO₂. Proximal anastomoses were performed with 4/0 double-ended continuous Prolene sutures and distal anastomoses were performed through standard groin incisions. Total operating and aortic cross-clamp times were measured as was the total blood loss for each procedure. Clinical outcome was also documented. Eight female laboratory-bred hounds underwent successful totally laparoscopic aortobifemoral bypass grafting, eight underwent open grafting, and eight underwent laparoscopic-assisted bypass. Mean operating time was 193 minutes in the animals undergoing totally laparoscopic insertion vs. 156 minutes in the open group and 180 minutes in the laparoscopic-assisted group. Aortic cross-clamping time was also significantly longer at 87 minutes vs. 43 minutes (p < 0.001)=" in=" the=" totally=" laparoscopic=" group,=" but=" blood=" loss=" was=" less.=" all=" eight=" laparotomy=" and=" laparoscopic-assisted=" dogs=" were=" still=" alive=" with=" no=" complications=" at=" 28=" days,=" whereas=" three=" of=" the=" eight=" in=" the=" totally=" laparoscopic=" group=" showed=" evidence=" of=" temporary=" paraplegia.=" this=" experimental=" study=" demonstrates=" that=" a=" totally=" laparoscopic=" approach=" can=" be=" used=" to=" insert=" a=" bifurcated=" aortofemoral=" bypass=" with=" a=" proximal=" end-to-end=" anastomosis=" but=" currently=" does=" not=" save=" time=" and=" may=" increase=" the=" risk=" of=" neurologic=">Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.     

Attempted rapid elbow flexion movements in patients with athetosis.

Voluntary rapid elbow flexion movements were studied in 14 patients with athetosis on the basis of cerebral palsy. When the movement was attempted with one arm, other muscles inappropriate for the task, such as muscles in the opposite limb, were also activated. EMG activity of the biceps and triceps was analysed in detail, and the patterns seen in the different patients were divided into six groups: (1) The normal "ballistic" triphasic pattern, with bursts of normal duration, alternating in biceps and triceps, but the triceps might be activated first, causing the limb to extend rather than flex, (2) The triphasic pattern, with bursts of long duration, (3) Repetitive cycles of the triphasic pattern with particularly long antagonist bursts, apparently limiting the movement in each cycle, (4) Long bursts synchronous in agonist and antagonist muscles, (5) Continuous activity of the agonist, with reduction in activity of the antagonist, (6) Failure to be able to do the task. The pathophysiology of athetosis is that voluntary movement is characterised by excessive muscular activity, most prominently in inappropriate muscles, both extraneous to the task and directly antagonistic.     

Adaptation to lateral displacement of vision in patients with lesions of the central nervous system

The visual-motor adaptation to lateral displacement of vision by prism glasses was studied in normal individuals and patients with cerebellar dysfunction, Parkinson's disease, right or left cerebral hemisphere lesions, Alzheimer's disease, or Korsakoff's syndrome. Adaptation was analyzed in two phases, the return to normal pointing with prism glasses in place (the "error reduction portion") and the mispointing in the opposite direction after the glasses were removed (the "negative aftereffect portion"). Negative aftereffect, which seems to be the best measure of true adaptation, was significantly reduced only for the cerebellar patients. This poor performance supports the involvement of the cerebellum in motor learning.     

Bone marrow transplantation depleted of T cells followed by repletion with incremental doses of donor lymphocytes for relapsing patients with chronic myeloid leukemia: a therapeutic strategy

BACKGROUND: For patients with chronic myeloid leukemia (CML), long-term survival after stem cell transplantation requires adequate control of graft-versus-host disease (GVHD) and disease recurrence. Relapsing patients respond to donor lymphocyte infusion (DLI) but develop life-threatening complications. METHODS: Patients with CML in first chronic phase received bone marrow (n = 14) or peripheral blood progenitor cell transplants (n = 4) from HLA-identical siblings. GVHD prophylaxis was by ex vivo T-cell depletion with CAMPATH 1G. If disease recurred, donors' mononuclear cells were collected by apheresis, the CD3 samples commencing at 10(6)/kg were aliquoted at half-log increment intervals, cryopreserved, and infused until disease clearance. RESULTS: Eighteen patients (median age: 32.5 years) received transplants. All engrafted without procedure-related mortality. Fourteen patients relapsed, and 13 entered the DLI program. Two developed extensive GVHD after single schedule infusions ranging from 89x10(6) to 670x10(6) mononuclear cells/kg, and one survives in complete remission (CR). The rest, treated with incremental dose DLI, experienced no acute toxicities. One, who had developed grade III steroid-responsive GVHD, died in CR2 from opportunistic infections. Steroids reversed limited cutaneous GVHD and elevated liver enzymes in five patients. Three others developed pancytopenia, and two restored blood counts only after donor peripheral blood progenitor cell infusions. Molecular CR2 was established in 12/13 patients, occurring in 10/11 (91%) on the incremental program at a median accumulation of 67 (range: 5-166) x10(6) CD3 cells/kg. Sixteen of 18 (89%) survive at median of 854.5 days from bone marrow transplantation, 4 in CR1 and 10 in CR2 at a median disease-free survival (for remission 2) duration of 341 days. The median combined disease-free survival of the 14 patients in CR 1+2 is 660 days, with 99% average performance status. CONCLUSIONS: Escalating DLI leads to safe new molecular CR in most CML relapse patients. These results raise the possibility of using "safe" transplantation programs of T-cell depletion, that include graded DLI as prevention against disease recurrence.