Search PubMed⌕ Search

Biomedical subjects

T A Miller

Publications and source records attributed to T A Miller.

At least 91 records · Page 5Linked to original sources
PubMed1996

Well-differentiated liposarcoma (atypical lipoma) of the lower extremity in a patient with bilateral leg lipodystrophy and lymphedema.

We present a report of a patient with bilateral lower extremity lipodystrophy and lymphedema who underwent excision of a large extremity liposarcoma. Total excision of the tumor was performed with no evidence of recurrence to date. The natural history, characteristics, and management of this tumor are discussed. A high index of suspicion and awareness among surgeons and pathologists should allow accurate diagnosis and treatment of this condition.

Female↗
PubMed1996

Cholecystokinin-induced protection against gastric injury is independent of endogenous somatostatin.

Cholecystokinin (CCK) prevents macroscopic injury to the stomach from luminal irritants by an unknown mechanism. The present study was undertaken in conscious rats to ascertain what role gastric mucosal blood flow, sensory neurons, and endogenous somatostatin play in CCK-induced gastric protection. Subcutaneous administration of CCK (10-100 micrograms/kg) significantly reduced macroscopic injury to the acid-secreting portion of the stomach caused by 1 ml of orally administered acidified ethanol (150 mM HCl, 50% ethanol) and augmented gastric mucosal blood flow (fluorescent microspheres) in a dose-dependent fashion. However, although the protective response to CCK (100 micrograms/kg) was still present at 2 h, the blood flow response had returned to baseline by 45 min. Ablation of capsaicin-sensitive afferent neurons with capsaicin (125 mg/kg sc) did not negate CCK-induced protection. Pretreatment with exogenous somatostatin (1 pmol-1 nmol/kg sc) failed to prevent the damaging effects of acidified ethanol to gastric mucosa. Immunoneutralization of endogenous somatostatin with somatostatin monoclonal antibody (2 mg ip) did not reverse the protective actions of CCK. Thus the data suggest that although CCK may prepare the gastric mucosa to withstand a damaging insult by augmenting gastric mucosal blood flow, its protective mechanism is independent of intact sensory neurons and endogenous somatostatin.

Animals↗
PubMed1996

Muscle force, perceived effort, and voluntary activation of the elbow flexors assessed with sensitive twitch interpolation in fibromyalgia.

OBJECTIVE: To measure maximal voluntary strength and central activation without fatigue, and to assess both peripheral and central components of muscle fatigue of the elbow flexor muscles, during exercise, in a group of patients with fibromyalgia (FM) (n = 11). Results are compared with data from control subjects (n = 36). METHODS: Maximal voluntary activation and strength of elbow flexors were quantified using twitch interpolation during attempted maximal isometric contractions both in unfatigued muscles and during fatigue produced by 45 min of submaximal exercise. RESULTS: Maximal voluntary strength of the elbow flexors before and during exercise was within the normal range. Central fatigue did not develop to a greater extent in the patient group. No patient had a decline in twitch amplitude during exercise below the 95% confidence limit for the decline in control subjects. However, the increment in perceived effort (Borg Scale) was abnormally large in 5 patients during the fatiguing exercise. CONCLUSION: Neither poor motivation, reflex pain inhibition, nor muscle contractile failure are important in the pathogenesis of fatigue in patients with FM. However, the subjective response to exercise is commonly excessive.

Adult↗
PubMed1995

Homonymous and heteronymous monosynaptic reflexes in biceps brachii.

Using poststimulus time histograms, it has been reported that stimulation of the median nerve at the elbow produces a monosynaptic EPSP in voluntarily active single motoneurons of the human biceps brachii. The present study was undertaken to: (i) determine whether such stimulation could evoke a reproducible reflex response in biceps brachii; and (ii) establish the optimal conditions for eliciting the reflex under clinical conditions. Twelve normal subjects were studied. No reflex response was recordable when biceps brachii was relaxed. A reflex response with a mean latency of 14.0 ms (+/- 0.96 ms) could be recorded during a background voluntary contraction. The response was small (0.5-4.5% of the maximal M wave) but symmetrical, and could be obtained in all subjects. The responsible afferents appear to be rapidly conducting fibers from forearm flexor muscles and the latencies of the response were consistent with a monosynaptic reflex. Reflex amplitude increased with stimulus intensity and contraction strength. Stimulus rate did not affect amplitude significantly. It is concluded that a reproducible heteronymous monosynaptic reflex can be recorded from the contracting biceps brachii on stimulation of the median nerve at the elbow. Although smaller than the homonymous H reflex evoked by stimulation at Erb's point, it was technically easier to demonstrate that the EMG potential was of reflex origin (rather than part of an M wave). These reflexes should be of value in the assessment of the C-5/C-6 segments and the upper trunk of the brachial plexus.

Adult↗
PubMed1995

Gastric mucosal high-energy phosphate metabolism. Influence of ethanol and PGE2.

This study investigated potential alterations in gastric mucosal energy metabolism following exposure to the damaging agent 50% ethanol (50% EtOH) alone and after pretreatment with either 16,16-dimethyl (dmPGE2) or the mild irritant 25% ethanol (25% EtOH). Fasted rats (n = 12-26/group) were orally given 1 ml of normal saline (NS), dmPGE2 in a dose of 5 micrograms/kg, or 25% EtOH. Fifteen minutes later, they randomly received 1 ml of NS or 50% EtOH. After 5 min, rats were anesthetized and their stomachs rapidly excised, frozen in liquid nitrogen, and lyophyllized. Once dried, the surface area (in square millimeters) of mucosal lesions was quantitated. Mucosa was then scraped off the underlying muscularis. Tissue metabolites (ATP, ADP, AMP, lactate, pyruvate, glucose, and glucose-6-phosphate) were measured in deproteinized, neutralized samples by enzymatic methods. In conjunction with the development of mucosal lesions involving an average of 45 mm2, ATP was significantly (P < 0.05) lower and AMP significantly higher in 50% EtOH-treated animals (indicating dephosphorylation) when compared with NS controls. Although both 25% EtOH and dmPGE2 prevented these lesions, only 25% EtOH prevented the ATP and AMP alterations. Fifty percent EtOH also significantly increased the tissue content of glucose and lactate over control values while glucose-6-phosphate was significantly decreased. With both protective agents pyruvate levels were significantly reduced, while glucose and lactate levels were not affected. In contrast to dmPGE2, the mild irritant (25% EtOH) significantly increased glucose-6-phosphate levels over control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1995

Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat. Role of endogenous prostaglandins.

Cholecystokinin is a gastrointestinal hormone known to physiologically regulate pancreatic protein secretion and gallbladder contractility. Some evidence suggests that cholecystokinin is also involved in the maintenance of gastrointestinal mucosal integrity. This study was undertaken to ascertain whether cholecystokinin could prevent the gastric mucosal injury induced by acidified ethanol and what role prostaglandins, and type A and type B cholecystokinin receptors might play in this process. Conscious, fasted rats were given subcutaneous saline or cholecystokinin octapeptide (10-100 micrograms/kg) 30 min before a 1-ml oral gastric bolus of acidified ethanol (150 mM HCl/50% ethanol). Five minutes later, rats were sacrificed and the total area of macroscopic injury quantitated (square millimeters). In additional experiments using a similar protocol, 1 ml of either the cyclooxygenase inhibitor, indomethacin (5 mg/kg), a type A cholecystokinin receptor antagonist, L-364,718 (0.01-1 mg/kg), or the type B cholecystokinin receptor antagonist, L-365,260 (12.5-25 mg/kg) was given intraperitoneally 30 min prior to pretreatment with cholecystokinin octapeptide. Cholecystokinin octapeptide dose-dependently prevented mucosal injury from acidified ethanol (corroborated by histology). The protective effect of cholecystokinin octapeptide was completely negated by L-364,718 and partially reversed by indomethacin, while L-365,260 had no discernible effect in this process. In a further study, cholecystokinin was unable to prevent the damaging effects of aspirin and the inhibition of endogenous prostaglandins. This, it appears that cholecystokinin is able to maintain mucosal integrity in the face of a damaging insult by activation of type A cholecystokinin receptors, an effect mediated, at least in part, through the release of endogenous prostaglandins.

Animals↗
PubMed1995

Terephthalic acid: a dosimeter for the detection of hydroxyl radicals in vitro.

Hydroxylation reactions of aromatic compounds have been used to detect hydroxyl radicals produced by gamma irradiation and ultrasound. The present study investigated the suitability of terephthalic acid (THA) as a hydroxyl radical dosimeter for general use in biologically relevant reactions. Hydroxyl radicals were generated by: (1) irradiating THA with a 254 nm ultraviolet light; (2) irradiating with gamma rays from a cesium source; and (3) generating hydroxyl radicals with 1 mM H2O2 and 10 microM Cu+2. In each of the three experiments, a fluorescent product was generated which exhibited identical fluorescent excitation and emission spectra. THA is non-fluorescent, eliminating the problem of a high initial background. Because THA has four identical ring hydrogens, only one mono-hydroxylated isomer was formed. The hydrogen peroxide reaction was dependent on the presence of a metal and cupric ions were effective in enhancing the reaction. With a Cu+2 concentration of 10 microM, the reaction was linear between 0-30 mM H2O2. Catalase abolished the reaction at a concentration of 100 micrograms/ml and the effects could still be observed at 10 ng/ml, consistent with the very high rate at which catalase destroys hydrogen peroxide. Tertbutyl- hydroperoxide did not generate any fluorescence in this system which makes THA a very specific detector of hydroxyl radicals.

Free Radicals↗
PubMed1995

Reproducibility of a heteronymous monosynaptic reflex in biceps brachii.

The present study provides normal data for a new technique to assess conduction across the C5/C6 segments by recording a heteronymous monosynaptic reflex response from the contracting biceps brachii in response to stimulation of the median nerve in the cubital fossa. The reflex responses were reproducible and symmetrical, with a mean latency of 14.8 msec (S.D. 1.4 msec) and an absolute side-to-side differences of 0.5 msec (S.D. 0.29 msec). Latency was significantly correlated with both age and height, and multiple regression analysis provided the following equation: latency (msec) = 0.091 x height (in cm) + 0.036 x age (years) - 1.988. Amplitudes had wide scatter (22-365 microV on the right side) and positive skew. An amplitude less than 40% of that for the other side would be outside the 90th percentile. Five cases are described to illustrate the potential clinical utility of this test. However, whether this reflex is of diagnostic value can be answered only by a prospective study comparing it with other routine investigations.

Adult↗
PubMed1995

Crystallographic structure of a peptidyl keto acid inhibitor and human alpha-thrombin.

The low molecular weight alpha-keto amide inhibitor CVS-1347, benzyl-SO2-Met(O2)-Pro-Arg(CO)((CONH)CH2)-phenyl, is a slow, tight binding inhibitor of alpha-thrombin amidolytic activity having a Ki = 1.28 x 10(-10) M. A complex between human alpha-thrombin and a hydrolysis product of CVS-1347 has been determined and refined using crystallography. The crystals belong to monoclinic space group C2 with cell dimensions of a = 71.08, b = 72.05 and c = 72.98 A and beta = 100.8 degrees. The structure was solved using isomorphous replacement methods and refined with resolution limits of (8.00-1.76) A to an R-value of 0.162. The Pro-Arg core of the inhibitor binds in the S2 and S1 subsites respectively, as is usually observed for Pro-Arg thrombin inhibitors. The Met(O2) side chain does not make any close contacts with the enzyme but influences the conformation of Glu192; the N-terminal benzylsulfonyl group makes an aromatic-aromatic contact with Trp215 in the hydrophobic part of the active site. The alpha-keto carboxylic acid of the proteolyzed inhibitor binds with the carboxylate group in the oxyanion hole, demonstrating that this region can accommodate an anion in a protease-peptide complex. The alpha-keto carbonyl group interacts closely with the two most important residues in the active site: the carbon atom is within a covalent bond distance of the active site Ser195 O gamma and the carbonyl oxygen is hydrogen bonded to His57.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Activity-dependent changes in impulse conduction in normal human cutaneous axons.

The present study was undertaken to determine if the axonal hyperpolarization produced by a brief train of impulses would impair neural transmission in cutaneous afferents of normal human subjects (n = 25). To assess changes in axonal excitability, a submaximal test stimulus was conditioned by a train of 10 supramaximal stimuli at 200 Hz. This produced a depression in excitability lasting up to 100 ms, demonstrable at nodes of Ranvier remote from the site of stimulus application, and probably due to activation of a slow K+ conductance. The effects of this change in excitability on neural transmission were assessed using a supramaximal test pulse. This revealed small but significant activity-dependent decreases in amplitude at conditioning-test intervals up to 20 ms and increases in latency at intervals up to 70 ms. Both the amplitude decrease and the latency increase were greater the longer the conduction distance. The reduction in amplitude of the compound sensory potential could be explained by temporal dispersion due to the increase in latency. It is concluded that, at the nodes of normal cutaneous afferents, the safety margin for impulse generation is sufficiently high that the activity-dependent hyperpolarization does not produce conduction block. It is likely that the previously described reductions in the amplitude of the compound sensory action potential in response to brief trains of stimuli were due to dispersion of the volley, not conduction failure, and that conduction failure does not occur in normal cutaneous axons solely by activation of slow K+ conductances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Hemorrhagic shock increases gut macromolecular permeability in the rat.

The effect of hemorrhagic shock on gut permeability to macromolecules was investigated using fluorescein isothiocyanate dextrans (4,300 or 73,100 daltons). These were given orally, then measured in systemic blood during hemorrhage (mean arterial pressure of 30 mmHg) and reperfusion; sham-shocked animals served as controls. Hemorrhage lasting 2 h resulted in a 5-fold increase in concentration of both tracers relative to that found in control groups. Reperfusion reduced these differences, with values approximately threefold greater than those of controls after 2 h. On a molar basis, the smaller molecule was more permeant than the larger one. This study provides evidence that hemorrhagic shock physically perturbs the normal barrier function of the mucosa, permitting very large substances in the gut lumen access to the circulation. It may further explain, at least in part, previous observations that hypovolemic shock results in bacterial translocation and endotoxemia.

Animals↗
PubMed1995

Protective effect of a 21-aminosteroid against hemorrhage-induced ischemia-reperfusion injury in the rat stomach: role of lipid peroxidation.

We investigated the role that lipid peroxidation plays in a hemorrhage-induced ischemia-reperfusion model of gastric injury. Rats were pretreated with an inhibitor of this process, a 21-aminosteroid (U-74389G, 10 mg/kg), or an appropriate control solution intravenously 15 min prior to 20 min of ischemia, followed by 20 min of reperfusion. Results indicated that U-74389G pretreatment significantly attenuated gastric damage compared with corresponding control animals (19.8 vs. 176.8 mm2, p < .001). Enaldehyde levels (picomoles/mg protein), a biochemical index of lipid peroxidation, paralleled these injury findings (12 vs 960, p < .001). Histologically, U-74389G pretreatment almost completely prevented gastric injury compared to control stomachs. Additional studies revealed that lipid peroxidation preceded the formation of gastric damage, and injury occurred predominantly during reperfusion, because animals subjected to ischemia alone without reperfusion failed to develop appreciable injury or enhanced enaldehyde formation. Further, if U-74389G was given intravenously after ischemia, but prior to reperfusion, gastric injury and enaldehyde formation were similarly attenuated. Our findings are consistent with the hypothesis that lipid peroxidation likely plays an important role in hemorrhage-induced ischemia-reperfusion injury to the stomach.

Animals↗
PubMed1995

H-reflexes in the upper extremity and the effects of voluntary contraction.

We report a simple technique for obtaining H-reflexes from the extensor carpi radialis (ECR) muscle. In 50 normal test subjects, above-elbow stimulation of the radial nerve evoked ECR H-reflexes, in all 100 arms with facilitation, and in only 8 without facilitation. H-waves were less common in extensor digitorum communis and rare in brachioradialis; these could have been volume-conducted ECR responses. Median-nerve stimulation at the elbow evoked H-reflexes in 92 of the 100 flexor carpi radialis (FCR) muscles; 44 of these required no facilitation. Background EMG (facilitation) activity or an overlapping M-wave often obscured the H-wave onset: among the onsets considered reliable in FCR (67/92) and ECR (84/100), mean latencies were 16.2 msec and 16.5 msec respectively, and correlated well with subject height and arm length. There was no significant difference in latency obtained with and without facilitation for the FCR H-reflexes and between techniques for the ECR H-reflexes. Right-left differences in latency ranged from 0 to 0.9 msec for ECR and 0 to 0.6 msec for FCR H-reflexes.

Adult↗