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Range of variations in motor unit potentials during reinnervation after traumatic nerve lesions in humans.

Successive stages in the reinnervation of denervated muscle fibers following a complete or partial motor nerve lesion in humans were analyzed with the concentric needle electrode during voluntary contraction. Motor unit potential (MUP) patterns were displayed by coherent EMG, in which the potential triggers an oscilloscope sweep and a digital delay line enables the early part of the MUP to be displayed. After a complete nerve lesion, MUPs showing the response of as few as one to three muscle fibers can be observed. MUPs become highly polyphasic as more muscle fibers are incorporated. Marked latency jitter and intermittent blocking of components as well as the occurrence of linked potentials result in complex patterns that may be confused with a "myopathic" pattern of brief small spikes if conventional observation of free-running sweeps is used alone. After a partial nerve lesion, the healthy motor axons achieve extensive collateral reinnervation of the denervated muscle fibers whereby linked potentials of various latencies are added after the original MUP. Adequate understanding of these characteristic features can help clarify some current issues in electromyography. The mechanisms by which long-latency linked potentials and desynchronized components are produced during remodeling of motor units in the course of regeneration involve a number of factors such as slow conduction along regenerated axon branches, ectopic motor end-plates, insecure neuromuscular transmission, and muscle fiber atrophy.

Adolescent↗

The raccoon as an animal model for upper limb neural prosthetics.

The raccoon was evaluated as an animal model for upper limb neural prosthetics. This animal was selected primarily because the functional use of its forelimb mimics in many ways the usage in humans and because of its optimal size and commercial availability. Eight cadaver and fresh specimen forearms were dissected. Important characteristics of the raccoon forearm were: 1) large muscles in the volar forearm, 2) large digits in the paw that appear more similar to humans than to other species such as cat or dog, 3) persistence of two median nerve cords into the forearm, 4) no separation of individual tendons of flexor digitorum superficialis and flexor digitorum profundus in the carpal tunnel, 5) a small thumb digit with little function and 6) a primary origin of flexor policis longus on the proximal ulna with a secondary origin on the radius. Four animals were anesthetized and responses of the forearm and paw to stimulation of the volar forearm muscles with percutaneous electrodes were evaluated. A pair of stimulating electrodes was placed in each of four muscles or muscle groups. Recording electrodes were placed in two muscles which showed the greatest separation of muscle movements to stimulation. Stimulation currents just above threshold produced discrete motion as well as recordable EMG M-waves. Incremental increases in stimulation current produced an increase in M-wave amplitude up to a maximal stimulating current. Torque recordings for pronation, wrist flexion and finger flexion showed graded and selective responses. These results including anatomical descriptions indicate both the limitations of this animal model and its potential use in the development of upper limb neural prosthetics. We conclude that the raccoon model may be superior to other nonprimate animal models such as the cat because of its extensive forearm and paw movements.

Animals↗

Effect of doublet impulse sequences in the crayfish claw opener muscles and the computer-simulated neuromuscular synapse.

The effects of doublet impulse sequences of the excitatory motor axon on the movement of the claw opener muscles in the crayfish were examined. The excitatory motor axon was stimulated electrically with various patterns of doublet impulse sequences generated by a digital computer. Doublet impulse sequences of stimulation produced a larger sustained movement than an uniform impulse sequences at the same mean rate of stimulation. The movement was largest when the interval between the impulses of a doublet was about 5 ms. This interval generated a movement amplitude 25% greater than that for the uniform impulse sequence. A simple model was formulated to stimulate the neuromuscular synapse of the claw opener muscle. The relationship between stimulation sequences with alternating long and short intervals and responses (firing probabilities) of the neuromuscular synapse at the same mean rate was investigated. The responses was classified into two typical types which are noneffective Type I and effective Type II to the absolute refractory period (ARP). The characteristics which are larger responses with short intervals in Type I and reduction of responses in the ARP region of Type II formed a plateau peak of the experimental results. By incorporating the reduction of end-plate potential (EPP) as a property of nonlinear rule for temporal summation into the model, it was shown that Type I response is maximal with a plateau peak at short interval, agreeing well with the experimental results from the claw opener muscles.

Animals↗

Manometry of the normal upper esophageal sphincter and its alterations in laryngectomy.

Rapid pull-through pressure profiles of the normal human upper esophageal sphincter (UES) were simultaneously studied with a conventional three-orifice Honeywell solid-state probe, an eight lumen radially perfused (RP) probe, and a circumferentially sensitive (CS) probe designed to measure UES pressure (UESP) without regard to probe orientation. Pressure curves were digitized and analyzed by computer. The Honeywell probe recorded significantly lower peak pressures than the other two methods, and had wide intrasubject pressure variations (average coefficient of variation, 53%). In contrast, UESP measured with the CS probe was constant for each subject (mean peak UESP, 121 mm Hg; average coefficient of variation, 15%). Anteroposterior RP probe UESP were identical to CS probe pressures. Thus, peak perfused anteroposterior UESP correlates with circumferentially measured sphincter squeeze.Computer programs were written that allowed RP probe pressures to be mapped in three dimensions. Normal three-dimensional maps were characterized by anteroposterior accentuation of peak pressures and also by consistent axial asymmetry with anterior peak pressures occurring 0.8+/-0.2 cm closer to the pharynx. After defining the normal two- and three-dimensional UESP configuration, patients who had undergone laryngectomy were studied. Peak pressures measured with the RP probe decreased to congruent with50 mm Hg and radial pressure asymmetry vanished. Like normals, CS probe pressures corresponded to peak RP probe pressures. UES length did not change significantly. Three-dimensional mapping showed that axial asymmetry also vanished. It therefore appears that the anatomic alterations produced by laryngectomy abolishes UESP asymmetry.

Adult↗

Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model.

Peroxidase-conjugated alpha-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in end-plates in external intercostal muscles of four patients with myasthenia gravis, in forelimb digit extensor muscles of rats with advanced chronic experimental autoimmune myasthenia gravis, and in suitable human and rat controls. In control end-plates, the previously reported localization of acetylcholine receptor on the terminal expansions of the postsynaptic folds and, in traces, on the presynaptic membrane was confirmed. By contrast, in myasthenia gravis some postsynaptic regions bound no P-BGT; in other regions, the folds displayed only faint traces of the reaction product, or only some segments of the postsynaptic membrane showed the reaction product; finally, in some regions there was no apparent decrease in reaction product. In general, those postsynaptic regions showing the greatest decrease in P-BGT binding were also the simplest or showed the most degenerative changes, and the presynaptic staining was decreased in proportion to the decrease in the adjacent postsynaptic P-BGT binding. In the experimental animals, the abnormalities in the amount and distribution of the acetylcholine receptor were essentially like those in the more severely affected patients. Morphometric estimates of the postsynaptic acetylcholine receptor surface correlated well with the patients' clinical status and linearly with the miniature end-plate potential amplitude.

Action Potentials↗

Lung surfactant secretion by interalveolar Ca2+ signaling.

Although clusters of alveoli form the acinus, which is the most distal respiratory unit, it is not known whether interalveolar communication coordinates acinar surfactant secretion. To address this, we applied real-time digital imaging in conjunction with photo-excited Ca2+ uncaging in intact alveoli of the isolated, blood-perfused rat lung. We loaded alveolar cells with the Ca2+ cage o-nitrophenyl EGTA-AM (NP-EGTA-AM) together with the fluorophores, fluo 4, or LysoTracker green (LTG) to determine, respectively, the cytosolic Ca2+ concentration ([Ca2+]cyt) or type 2 cell secretion. To uncage Ca2+ from NP-EGTA, we exposed a region in a selected alveolus to high-intensity UV illumination. As a result, fluo 4 fluorescence increased, whereas LTG fluorescence decreased, in the photo-targeted region, indicating that uncaging both increased [Ca2+]cyt and induced secretion. Concomitantly, [Ca2+]cyt increases conducted from the uncaging site induced type 2 cell secretion in both the selected alveolus as well as in neighboring alveoli, indicating the presence of interalveolar communication. These conducted responses were inhibited by pretreating alveoli with the connexin43 (Cx43)-inhibiting peptides gap 26 and gap 27. However, although the conducted [Ca2+]cyt increase diminished with distance from the uncaging site, type 2 cell secretion rates were similar at all locations. We conclude that Cx43-dependent, interalveolar Ca2+ signals regulate type 2 cell secretion in adjacent alveoli. Such interalveolar communication might facilitate acinar coordination of alveolar function.

Aniline Compounds↗

Predictive value of fundus autofluorescence for development of geographic atrophy in age-related macular degeneration.

PURPOSE: It has been suggested that lipofuscin accumulation, as measured by increased fundus autofluorescence (FAF), precedes progression or development of junctional zone geographic atrophy (GA) in age-related macular degeneration (AMD). The tools of biomedical image analysis were used to measure the probabilistic relationship of GA progression to increased FAF. METHODS: Serial AF images of eight eyes of six patients with AMD with GA were registered on computer. The images were leveled with a 12-zone quadratic polynomial mathematical model to minimize background variability. Semiautomated segmentation of GA was performed on the leveled images. Increased FAF was defined as a gray level greater than 2 standard deviations above the leveled image mean, identified on the initial image with automated segmentation, and measured as a fraction of the 250-microm border zone surrounding the initial GA lesion. Areas of GA lesions were identified on the final image. The positive predictive value (PPV) of increased FAF was determined as the probability that any pixel with increased FAF in the initial image would become part of new GA in the final image. Relative PPV was determined relative to the total quantity of new GA. The NPV (NPV) of increased FAF was calculated as the probability that any pixels without increased FAF would not become atrophic. The relative NPV was determined similarly. A similar analysis was also conducted with a 500-microm border zone to determine the predictive value of proximity to the original GA lesion ("proximity") for GA progression. RESULTS: As a fraction of the geographic atrophy border zone, the mean new GA was 0.44+/-0.20, and the mean increased FAF was 0.06+/-0.06. The mean PPV of increased FAF for new GA formation was 0.50+/-0.26. Compared with the relative PPV of chance of 1.0, the mean relative PPV of increased FAF was 1.15+/-0.28. The mean NPV of increased FAF was 0.57+/-0.20. The mean relative NPV of increased FAF was 1.00+/-0.02. In the 500-microm border zone, the mean relative PPV of FAF and of proximity were essentially equal (1.56+/-.70 and 1.52+/-0.26, respectively), whereas the mean relative NPV of proximity was significantly greater than that of FAF (1.26+/-0.19 and 1.01+/-0.01, respectively, P=0.02) CONCLUSIONS: The results of digital image analysis suggest that although increased FAF may have a modest PPV for new GA development, the relative PPV is generally no greater than chance. Similarly, the relative NPV demonstrates negligible difference from chance and is also lower than the relative NPV of proximity. This suggests that increased FAF, though a disease manifestation, is not a strong risk factor for development or extension of GA.

Aged↗

Midterm results of uterine artery embolization for symptomatic adenomyosis: initial experience.

PURPOSE: To prospectively evaluate the midterm results of uterine artery embolization for symptomatic adenomyosis. MATERIALS AND METHODS: The study protocol was approved by the institutional review board, and all participants gave written informed consent. Eighteen women (mean age, 44.3 years) with symptomatic adenomyosis were treated with bilateral embolization of the uterine arteries. The diagnosis of diffuse adenomyosis was based on heterogeneous abnormal myometrial echogenicity with myometrial cysts at ultrasonography (US) or on enlarged junctional zone and myometrial cysts at magnetic resonance (MR) imaging. Focal adenomyosis was diagnosed if there was a circumscribed nodular lesion mimicking intramural fibroid. All patients with associated uterine fibroids were excluded. Embolization was offered as an alternative to hysterectomy in all women. Clinical evaluation was made at regular intervals to assess patient outcome. Follow-up US or MR imaging was performed 6 months after embolization to assess uterine volume reduction. RESULTS: Bilateral uterine artery embolization was achieved in all but one woman by using polyvinyl alcohol particles or trisacryl microspheres. All women resumed normal menstruation after the procedure. After 6 months, 15 (94%) of 16 women reported improvement in menorrhagia. Follow-up images at 6 months depicted a slight decrease (mean, 15%) in uterine volume in 17 (94%) of 18 women. After 1 year, 11 (73%) of 15 women had improvement in menorrhagia, and eight (53%) of 15, complete resolution. After 2 years, five (56%) of nine women had complete resolution of menorrhagia. Eight (44%) of 18 women required additional treatment during follow-up for failure or recurrence; five women (28%) underwent hysterectomy. CONCLUSION: Even if short-term results of uterine artery embolization to treat adenomyosis appear encouraging, midterm results are disappointing, with only 55% of treated patients showing clinical improvement after 2 years.

Adult↗

Utility of static pressure ratio recording during angioplasty of arteriovenous graft stenosis.

Intra-access static pressure ratio (SPR) (intra-access pressure/mean arterial pressure) can be measured during angioplasty (PTA) to assess the functional importance of an arteriovenous graft (AVG) stenosis. We used SPR in 70 patients with AVGs who underwent 98 angioplasty procedures. SPR was measured during angioplasty by placing a catheter tip at mid-access. Inflow stenosis (IF) = stenosis proximal to the tip of the catheter. Outflow stenosis (OF) = stenosis distal to the tip of the catheter up to the superior vena cava-atrial junction. Post PTA, access flow (Qa) was assessed within 2 weeks. Complete data sets for both SPR and Qa were available in 83 procedures. Using a normal SPR ratio of 0.3-0.4 at mid-graft, three patterns of SPR were noted. In 63 of 83 (76%) cases SPR was elevated prior to PTA (0.71 +/- 0.13 SD). PTA reduced SPR toward normal range (0.44 +/- 0.12) in 53 cases (84%). In the remaining 10 (16%), SPR decreased to a low value (0.22 +/- 0.03) and normalized (0.40 +/- .0.11) only after PTA of a coexisting inflow stenosis. In 12 of 83 (14%) procedures, the initial SPR was low (0.18 +/- 0.04) and increased toward normal (0.3 +/- 0.08) following IF stenosis PTA in seven (58%) cases. For the remaining five (42%) cases SPR increased to a high value (0.70 +/- 0.21) and decreased toward normal range (0.33 +/- 0.07) only after OF stenosis angioplasty. In 8 of 83 (10%) procedures, initial SPR was normal (0.33 +/- 0.02). Angiography revealed coexisting IF and OF stenoses. SPR remained within the normal range after PTA of these lesions (0.33 +/- 0.02). Qa increased significantly in 74 of 83 (89%) procedures (before = 572 +/- 201, after = 1109 +/- 368 ml/min; p < 0.001). SPR measurements can assist in hemodynamic assessment of an AVG during angioplasty procedure.

Aged↗

Coordinated gastric and sphincter motility evoked by intravenous CCK-8 as monitored by ultrasonomicrometry in rats.

Gastric and sphincter motility evoked by intravenous injection of CCK-8 were investigated in urethane-anesthetized rats. Digital ultrasonomicrometry was used to monitor pyloric (PYL), antral (ANT), corpus (COR), and lower esophageal sphincter (LES) movements while simultaneously measuring intragastric pressure (IGP) and, in some experiments, subdiaphragmatic intraesophageal pressure (sIEP). Intracrystal distances (ICD) were measured continuously between pairs of piezoelectric crystals affixed to the serosa of PYL, ANT, COR (circular and longitudinal), and LES. Consecutive intravenous injections of CCK-8 (0.3, 1, and 3 microg/kg) at 30-min intervals caused dose-dependent simultaneous tonic contractions of PYL and ANT, LES opening, and drops in IGP with peak changes at 3 microg/kg of -17.9 +/- 2.1, -7.7 +/- 2.5, 6.5 +/- 1.4, and -29.2 +/- 3.8%, respectively, whereas intravenous saline had no effect. Rhythmic contractile activity was inhibited by CCK-8. COR responses were not significantly different from vehicle controls for most metrics, and the direction of response for circular COR varied between preparations, although not for repeated trials in a single preparation. During the LES response to CCK-8, sIEP rose in parallel with drops in IGP, indicating formation of a common cavity. Recovery of LES ICD after intravenous CCK occurred more rapidly than recovery of PYL ICD, suggesting the importance of preventing simultaneous patency of gastroesophageal and gastroduodenal passages. The CCK(A) receptor antagonist devazepide (500 microg/kg intravenous) inhibited motion responses evoked by intravenous CCK-8. These data revealed CCK-8-induced gastric and sphincter activity consistent with retropulsion of gastric content.

Animals↗

Formation and survival of a postsynaptic specialization in cultures of embryonic Xenopus nerve and muscle cells.

The formation and survival of nerve-induced clusters of acetylcholine receptors (AChRs) was monitored over a synaptogenic period of several days in cultures of myotomal muscle cells and spinal cord neurons derived from embryos of Xenopus laevis. AChRs were labeled with fluorescent alpha-bungarotoxin so that neurite-associated receptor patches (NARPs) could be viewed at daily intervals throughout the neuritic arbor of selected neurons. To avoid bleaching the NARPs and damaging the neurons, the intensity of the fluorescence excitation was reduced to 3%. Images were digitized and NARPs were measured with a computer-based image analysis system. Virtually all newly formed NARPs (greater than 90%) were detected at the same time as neurite-muscle contact and in the same proximal-distal sequence as neuritic growth. Those which formed in 6- to 13-day-old cocultures had similar distributions with respect to length, area, intensity, and area X intensity to those which formed in 1- to 2-day-old cocultures. NARPs exhibited variable daily changes in these parameters but on average they grew and reached close to their ultimate values within 1-2 days. Almost all (greater than 95%) survived as long as their contacts. In cases where NARP formation occurred on the same muscle on 2 or more different days, the ones which formed first were the most extensive. Spontaneous neurite withdrawal occurred mainly from young NARPs and resulted in their rapid disappearance. It is suggested that during the period when neurons grow and make new contacts with muscle cells there is no substantial change in their capacity to trigger the formation of new synaptic sites and maintain preexisting ones, and that the first-forming synapses on a muscle cell tend to be the largest because muscle cells have a limited capacity to generate postsynaptic membrane. Additional implications of the findings for synapse formation and elimination are discussed.

Animals↗

A biomechanical comparison of multistrand flexor tendon repairs using an in situ testing model.

An in situ testing model was used to evaluate the performance of zone II flexor tendon repairs and to compare the biomechanical properties of 4-strand repairs with 2- and 6-strand repairs. Fifty digits from human cadaveric hands were mounted in a custom apparatus for in situ tensile testing. Intratendinous metallic markers were placed so that gap formation could be determined by fluoroscopy during tensile testing. Three 4-strand repairs (the 4-strand Kessler, the cruciate, and a locked modification of the cruciate repair) were compared with the 2-strand Kessler and the 6-strand Savage repairs. Ultimate tensile strength, load at 2-, 3-, and 4-mm gap formation, and work of flexion were determined. Work of flexion, while increased for the multistrand repairs, did not show a statistically significant correlation with the number of strands crossing the repair site. The tensile strength of the 6-strand repair was significantly greater than each of the 2- or 4-strand repairs. The tensile strength of all 4-strand repairs was significantly greater than the 2-strand repair. The 6-strand repair and the 2 cruciate repairs demonstrated a statistically increased resistance to gap formation compared with the 2-strand Kessler repair, but notably there was no statistically significant difference in gap resistance between the 2and 4-strand Kessler repairs. This in situ tensiletesting protocol demonstrated that 4- and 6-strand repairs have adequate initial strength to withstand the projected forces of early active motion protocols. Three of the 4 multistrand repairs demonstrated improved gap resistance compared with the 2-strand repair. The presence of the second suture in the Kessler configuration significantly increases its strength but not its gap resistance.

Analysis of Variance↗

Barrett's metaplasia and adenocarcinoma of the esophagus in scleroderma.

Gastroesophageal reflux is well documented in scleroderma, but the complications of Barrett's metaplasia and adenocarcinoma are not well described. The records of 75 patients with scleroderma seen over a four-year period at the Hospital of the University of Pennsylvania were retrospectively reviewed to determine the prevalence of Barrett's metaplasia and adenocarcinoma of the esophagus and to identify clinical, manometric, laboratory, or radiographic criteria that might predict the presence of these lesions. Twenty-four of these patients underwent endoscopy. In this group, the prevalence of Barrett's metaplasia was 37 percent (nine patients) and adenocarcinoma was also present in two of these patients. The patients with and without Barrett's metaplasia were similar in age (range, 22 to 64 compared with 28 to 79, respectively), sex (six of nine compared with 12 of 15 female, respectively), frequency of esophageal motility disorders, presence of proximal skin involvement, digital ulceration, and pulmonary involvement as measured by diffusion capacity. Barrett's metaplasia was diagnosed on the basis of double-contrast esophagographic results in only one of eight patients with Barrett's metaplasia so-studied. Patients with Barrett's metaplasia tended to have longer duration of heartburn (90 +/- 40 months compared with 11 +/- 35 months) and dysphagia (39 +/- 22 months compared with 7 +/- 3 months). Patients with Barrett's metaplasia also tended to have greater impairment of lower esophageal sphincter pressure either at end-expiration (4.0 +/- 2.1 compared with 6.1 +/- 1.8 mm Hg) or mid-respiration (13.0 +/- 3.0 compared with 16.9 +/- 2.5 mm Hg). Using chi-square analysis, however, none of these differences reached statistical significance. Discrimination did occur on the basis of the presence of the CREST (calcinosis, Raynaud's phenomenon, esophageal manifestations of scleroderma, sclerodactyly, and telangiectasis) variant (55 percent compared with 7 percent, p less than 0.01), a duration of dysphagia of more than five months (p less than 0.03), and mid-respiratory lower esophageal sphincter pressure of less than 10 mm Hg (p less than 0.05). It is suggested that: Barrett's metaplasia of the esophagus occurs in one third of patients with scleroderma; clinical, manometric, laboratory, and radiographic features are poor predictors of the presence of Barrett's metaplasia; patients with CREST syndrome, prolonged dysphagia, or a very low lower esophageal sphincter pressure may have an increased risk for the development of metaplasia; patients with scleroderma and Barrett's metaplasia have an increased risk of complications such as stricture or adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Pharmacological characterization of noradrenaline-induced contractions of the porcine isolated palmar lateral vein and palmar common digital artery.

1. The aim of this study was to examine the pharmacological characteristics of alpha-adrenoceptor-mediated contractions in two porcine isolated blood vessels, the palmar lateral vein (PLV) and the palmar common digital artery (PCDA). This was carried out with noradrenaline used as the agonist throughout, and either phentolamine (non-selective alpha-adrenoceptor antagonist), prazosin and YM-12617 (selective alpha 1-adrenoceptor antagonists) or rauwolscine and CH-38083 (selective alpha 2-adrenoceptor antagonists). 2. Noradrenaline (0.003-10 microM) produced concentration-dependent contractions in both vessels, with the PCDA (pD2 = 6.33 +/- 0.07, n = 10) being approximately 10 fold less sensitive to noradrenaline compared to the PLV (pD2 = 7.39 +/- 0.09, n = 8). Also, the maximal response to noradrenaline was greater in the PCDA compared to the PLV. Phentolamine (0.03-30 microM) produced parallel rightward shifts in the CRC to noradrenaline in both tissue preparations. The pA2 values were similar and slopes of the Schild plots were not significantly different from unity, indicating an interaction between phentolamine and a single receptor in each preparation. 3. In the PCDA the alpha 1-adrenoceptor antagonists, prazosin (0.01-1 microM) and YM-12617 (0.01-1 microM) produced non-parallel rightwards shifts in the CRC to noradrenaline, with the lower 10-15% of the CRC exhibiting greater resistance to the effects of these antagonists compared to the upper part. In contrast, rauwolscine (1-10 microM) and CH-38083 (10 microM) produced parallel displacement of the CRC to noradrenaline. In the PLV, low concentrations of either alpha l- (0.01 microM) or alpha2-adrenoceptor antagonists(0.1-1 microM) produced a large shift in the CRC, but subsequent higher concentrations had only small additional effects. Based upon pKB values estimated from the effects of the lower concentrations of antagonists, the results are consistent with a large population of alpha1-adrenoceptors in the PCDA and a mixture of alpha l- and alpha2-adrenoceptors in the PLV.4. In both tissues, when an ac,- and an a2-adrenoceptor antagonist were used in combination the effect produced was greater than that with either agent alone. In contrast, the combination of the alpha1-adrenoceptor antagonists (prazosin and YM-12617 together) or the alpha2-adrenoceptor antagonists (CH-38083 and rauwolscine together) were no more effective than that produced by the individual antagonists. These findings suggest the presence of functional alpha l- and alpha2-adrenoceptors in the PLV andPCDA.5. Phenoxybenzamine (0.3-3 microM, 60min exposure) produced a concentration-dependent reduction in the maximal response to noradrenaline which was more pronounced in the PCDA than the PLV. After a 60 min exposure to a combination of phenoxybenzamine (1 microM) and rauwolscine (1 microM), the remaining NA-induced contraction after washout was resistant to prazosin (0.1 microM) and sensitive to rauwolscine(1 microM) in both tissue preparations, indicating the existence of functional alpha2-adrenoceptors in both vessels.6. Evidence suggests that post-junctional alpha l- and alpha2-adrenoceptors contribute to noradrenaline-induced contractions in the PCDA and PLV, with the latter possessing a larger population of functional alpha2-adrenoceptors.

Adrenergic alpha-Antagonists↗

[Study on the latency difference between compound muscle and sensory nerve action potentials].

In motor nerve conduction studies compound muscle action potentials (CMAPs) appear later than sensory nerve action potentials (SNAPs). This time lag originates from the conduction delay at the distal motor axon, neuromuscular transmission time and muscle action potential induction time. To investigate the latency difference between CMAPs and SNAPs we studied 46 healthy individuals, 46 patients with diabetes mellitus and 33 patients with carpal tunnel syndrome, using the lumbrical and interossei recording method. In this method the recording active electrode was placed on the 2nd lumbrical muscle and the reference electrode on the proximal palmar aspect of the index finger. Supramaximal stimulation was given to the median or ulnar nerve trunk at 9-cm proximal to the recording active electrode. The CMAP from the 2nd lumbrical muscle (L) and the SNAP from the digital nerve (N) were recorded after median nerve stimulation, and the CMAP from the 2nd interossei muscles (I) was recorded after ulnar nerve stimulation. The residual latency, which is arbitrary defined as the latency difference (L-N) in this study, was 1.38 +/- 0.15 (mean +/- SD) msec in healthy individuals. About 1 msec of the residual latency is regarded as the time for neuromuscular transmission and the time to evoke muscle activities. Thus, the conduction delay at the distal motor axon was calculated as about 0.4 msec in healthy individuals. The residual latency was relatively constant in 29 diabetic patients without conduction delay across the carpal tunnel, which was defined by the latency difference (L-I) < or = 0.4 msec. Their sensory nerve conduction velocities (calculated from N latency) were always above 40 m/sec. On the other hand in diabetic patients with conduction delay across the carpal tunnel, which was defined by the latency difference (L-I) > 0.4 msec, the residual latency gradually increased as the sensory nerve conduction velocity decreased. Their sensory nerve conduction velocities were mostly less than 40 m/sec. The similar relationship was observed in patients with carpal tunnel syndrome without diabetes mellitus. We consider that the diabetic neuropathy alone doesn't cause the increase of the residual latency. Instead, severe conduction delay across the carpal tunnel decreases the N velocity and increases the residual latency. We can also regard the relationship between the latency difference (L-N) and N velocity as being in inverse proportion. Perhaps the increase of the residual latency was simply caused by the proportional decrease in the conduction velocity at the distal motor axon, not by the special mechanism concerning to the carpal tunnel syndrome. This paper presented the electrophysiological changes seen in the distal segment secondary to the proximal entrapment.

Action Potentials↗

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗