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Biomedical subjects

T A Miller

Publications and source records attributed to T A Miller.

At least 145 records · Page 8Linked to original sources

The effects of dynamic tension and reduced graft size on muscle regeneration in rabbit free muscle grafts.

In a study of 28 adult New Zealand White rabbits, the influence of tension and size on muscle regeneration in tibialis anterior free muscle grafts (without vascular anastomoses) was examined 6 months after transplantation. Three laboratory models were studied: (1) whole dynamic (WD) graft (allowing ankle excursion and, therefore, variable dynamic physiologic tension), (2) whole static (WS) graft (constant, fixed length and, thus, only isometric tension), and (3) longitudinally sliced (reduced radius) dynamic (SD) model. Bilateral orthotopic grafts of the tibialis anterior muscle were performed in 24 rabbits (eight animals in each of the three different model groups). Controls consisted of normal tibialis anterior muscle from four age-matched rabbits. All tibialis anterior muscle grafts were examined histologically (fiber counts) and functionally (determined by in situ contractile properties under maximal stimulation conditions). The WD grafts demonstrated a significantly higher number of regenerated fibers per muscle cross section (4819 +/- 589) than the WS (2221 +/- 603) or SD (1919 +/- 732) grafts. The amount of tetanic tension in the WD grafts was 35 percent of the control and twice as much as that of the WS grafts (WD 1.0 +/- 0.2 kg versus WS 0.5 +/- 0.4 kg; p less than 0.05). The SD grafts produced approximately one-third as much maximum tetanic tension as the WD grafts (0.3 +/- 0.1 kg versus 1.0 +/- 0.2 kg), demonstrating that the amount of recovery was similar in these two dynamic models, since only the longitudinal middle third of the muscle was grafted in the SD model. Free muscle grafts under dynamic tension, which allows excursion, have shown a greater amount of muscle-fiber regeneration and restoration of function compared with a graft with fixed length. The positive effect of dynamic mechanical tension on small autogenous free muscle grafts (without vascular anastomoses) is clinically significant in the reconstruction of facial and hand neuromuscular deficits when blood vessels are not available for reanastomosis. Future studies using the tibialis anterior WD and SD transplant models will strengthen our understanding of the events of spontaneous revascularization and skeletal muscle regeneration.

Analysis of Variance↗

Lymphedema.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in plastic surgery. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in plastic surgery that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Plastic Surgery of the California Medical Association, and the summaries were prepared under its direction.

Humans↗

Effects of alcohol on lectin binding affinity in rat gastric mucosa.

Fluoresceinated lectins were employed to qualitatively evaluate cell surface carbohydrates, with and without ethanol exposure, in rat stomach mucosae. Rats received 1 ml of saline, or 50% or 100% ethanol orally. After 30 min, tissue samples of the glandular stomach were retrieved, cryosectioned, and incubated with one of a panel of lectins. Another set of sections was preincubated with neuraminidase to remove sialic acid residues. Qualitative evaluation of lectin binding showed that although several different sites stained, concanavalin A was the only lectin to stain the extracellular matrix, and soybean agglutinin the only lectin to stain chief cells. Neuraminidase preincubation enhanced lectin binding to both stained and previously unstained sites. Ethanol, both 50% and 100%, produced changes in both neuraminidase-treated and untreated tissues, increasing the specific binding of concanavalin A, Ulex europaeus agglutinin I, and wheat germ agglutinin, while decreasing Helix pomatia agglutinin and soybean agglutinin. These results suggest that ethanol can, through unknown mechanisms, alter carbohydrate binding affinity.

Animals↗

Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels.

Previous studies of hypothermia and blood coagulation have focused on alterations in the levels of blood clotting elements using coagulation tests performed under normothermic conditions. However, because of the enzymatic nature of activated clotting factors, hypothermia should also be expected to affect clotting factor activities. Multiple determinations of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on commercially available normal human plasma at assay temperatures similar to those encountered clinically (25-37 degrees C). Both the APTT and the PT were significantly prolonged at temperatures below 35 degrees C (P less than 0.05). Clotting time correlated significantly with assay temperature in a negative exponential fashion for all three tests (r = -0.97 for APTT, -0.93 for PT, -0.71 for TT, P less than 0.001 for all regressions). Clotting time prolongation appears proportional to the number of enzymatic steps involved. These data indicate that the coagulopathy observed during hypothermia is, in part, independent of clotting factor levels.

Blood Coagulation↗

Prostaglandin prevents aspirin injury in the canine stomach under in vivo but not in vitro conditions.

This study compared the ability of topical 16,16-dimethyl prostaglandin E2 in a dose range of 0.3-3.0 micrograms/ml to prevent aspirin-induced injury in the canine stomach under both in vivo and in vitro conditions. For in vitro studies, isolated strips of oxyntic mucosa were exposed to 10 or 20 mM aspirin (ASA) at pH 1-4, with and without treatment with 16,16-dimethyl prostaglandin E2. For in vivo experiments, a portion of the oxyntic stomach was mounted between the rings of a Lucite chamber, with splenic vessels intact, such that the mucosa was divided into halves. Both sides were exposed to 20 mM ASA at pH 1 or 2, and one side also received concomitant treatment with 16,16-dimethyl prostaglandin E2. After ASA exposure, tissue samples were prepared for quantitative microscopic analysis of the degree of injury. Under both experimental conditions, the magnitude of gastric injury by ASA was pH-related, being most pronounced at pH 1; this damage was worse under in vitro conditions, and both concentrations of ASA were equally damaging in this setting. 16,16-Dimethyl prostaglandin E2 failed to prevent ASA injury in vitro at any pH and ASA concentration tested, but markedly reduced the magnitude of injury in vivo. The most effective protective dose of 16,16-dimethyl prostaglandin E2 under in vivo conditions was 1.0 micrograms/ml. The diminished tolerance to ASA damage in vitro when compared with in vivo, and the inability of 16,16-dimethyl prostaglandin E2 to prevent these damaging effects in vitro, underscores the probable crucial role for blood flow, and possibly neural innervation, in mediating the protective effects of prostaglandins.

16,16-Dimethylprostaglandin E2↗

Prostaglandin-induced gastric mucosal protection against stress injury. Absence of a relationship to tissue glutathione levels.

The effects of 16,16 dimethyl prostaglandin E2 (dmPGE2) on the gastric mucosa of rats subjected to 1, 2, and 24 hours of water immersion stress were examined histologically. Results indicated a time-related increase in the total percentage length of glandular mucosa injured in normal saline (NS) pretreated rats that was significantly attenuated by subcutaneous dmPGE2 pretreatment (5 micrograms/kg) after 1 hour (46.0 +/- 12.9 vs. 16.8 +/- 2.3; p less than 0.005), 2 hours (45.4 +/- 1.0 vs. 13.8 +/- 2.2; p less than 0.001), and 24 hours (93.1 +/- 2.6 vs. 65.1 +/- 7.0; p less than 0.005) of water immersion stress. Moreover, dmPGE2 essentially prevented the occurrence of deep, glandular injury that, in NS controls, involved approximately 13% and 26% of the mucosal surface after 2 and 24 hours of immersion stress, respectively. Additionally, tissue levels of glutathione (mumole/g weight of wet tissue) were measured to determine its role under such conditions. After 1 hour of stress, there were no differences in glutathione levels between NS or dmPGE2 pretreated animals and fasted controls. After 2 and 24 hours of stress, there were likewise no differences in glutathione levels between NS and dmPGE2 pretreated groups, although levels in both groups were significantly decreased from fasted controls by approximately 30% at 2 hours and 37-47% after 24 hours. These histologic and biochemical data indicate that dmPGE2 attenuates both the extent and depth of glandular mucosal injury and does so in a manner unrelated to alterations in glutathione levels in gastric epithelium.

16,16-Dimethylprostaglandin E2↗

Microscopic correlates of adaptive cytoprotection in an ethanol injury model.

The present study histologically investigated the efficacy of pretreating rat gastric mucosa with the mild irritants, 10% and 25% ethanol (EtOH), against the known damaging effects of 100% EtOH. Fasted rats received 1 ml of either water, 10% EtOH, or 25% EtOH by orogastric intubation. Fifteen minutes later, a portion of these animals was sacrificed and tissue samples of the oxyntic region of the stomach were excised and processed for quantitative histologic analysis. Remaining animals received a 1 ml oral bolus of the necrotizing agent, 100% EtOH. Five minutes later, these animals were sacrificed and tissues were prepared in a like manner. In a separate series of experiments, the aforementioned protocols were repeated, except that all animals received the prostaglandin synthetase inhibitor, indomethacin (5.0 mg/kg intraperitoneally), 30 min before administration of the mild irritant. Microscopically, the administration of water or 10% EtOH alone caused a small and comparable amount of superficial injury to the gastric mucosa. Moreover, both substances failed to induce protection in stomachs subsequently exposed to 100% EtOH. Indomethacin pretreatment did not significantly alter any of these findings. In marked contrast, 25% EtOH alone elicited a substantial degree of superficial damage to the gastric mucosa. Nevertheless it significantly reduced the depth of injury in animals subsequently challenged by 100% EtOH. Indomethacin failed to aggravate the effects of 25% EtOH alone, but partially inhibited the protective effect of this mild irritant against 100% EtOH induced damage. Our findings indicate that adaptive cytoprotection is a real phenomenon that can be demonstrated microscopically. Such protection is limited primarily to the deep mucosal layers (i.e. gastric glands), appears in part to be prostaglandin mediated and seems to require the generation of moderate surface cell damage (as occurred with 25% EtOH, but not 10% EtOH) to induce its initiation.

Animals↗

Mechanisms of resistance to pyrethroid insecticides.

In the 10 years or so since the photostable pyrethroid insecticides such as permethrin and fenvolerate were introduced, this family of compounds has become widely used to control agricultural pests, and finds increasing usage to control arthropods of medical and veterinary importance. The synthetic pyrethroids offer many advantages for veterinary and public health use, particularly their selectivity, high toxicity to insects, and relative lack of chronic effects. They are also inherently stable, and so have become widely used as residual sprays on house walls to control insects in the domestic environment. But as with other classes of insecticides such as organochlorines, organophosphotes and carbamates, resistance to pyrethroids is now increasingly reported. In this article, Tom Miller explains the principle mechanisms of resistance to pyrethroids, using the North American horn fly (Haematobia irritans) as an example now showing many common resistance traits.

Journal Article↗

Therapeutic and functional results of limb salvage to treat sarcomas of the forearm and hand.

Twenty-six patients with soft tissue sarcomas of the forearm and hand were treated with limb salvage protocols involving surgical wide excision, chemotherapy, and radiation therapy. Six received immediate or delayed reconstructive surgery to improve function. The average delay from the time of the first medical consultation until the correct diagnosis was made was 4.5 months. The average follow-up period was 44 months; a 91% survival rate was observed, with an 8% rate of local recurrence. Functional abilities were assessed by a questionnaire concerning work, household activities, and overall satisfaction with the surgical result. Eight-six percent of the patients had an excellent functional result, and 84% reported excellent satisfaction with their operation.

Adolescent↗

Ultrastructural aspects of prostaglandin cytoprotection in an alcohol injury model.

The effects of absolute ethanol (EtOH) and 16,16-dimethyl-prostaglandin E2 (PGE2) on the ultrastructure of rat gastric mucosa were assessed using standard electron microscopic techniques. Fasted rats were injected subcutaneously with 10 micrograms/kg body weight of PGE2 or saline. After 30 min, animals received orally 100% EtOH or an equal volume of saline. Gastric mucosa was sampled at 5 min and 1, 2, 8, and 24 h post-EtOH and tissues procured for scanning and transmission electron microscopy. Both mucosal epithelial and connective tissue compartments were assessed. At 5 min after EtOH, in saline-pretreated animals, tissues showed extensive destruction of epithelium and connective tissue; major breaks in the basal laminae were coincident with hemorrhage. Deep-lying epithelial cells and most of the basal lamina were spared in tissues exposed to PGE2 prior to EtOH, permitting nearly complete repair within 24 h. Restitution proceeded over small breaks or pleats of basal lamina but failed in regions of total destruction of this structure. These data indicate that PGE2 protects not only deep-lying epithelial cells from EtOH damage but associated connective tissue as well and that sparing of both compartments leads to orderly and rapid epithelial restitution.

16,16-Dimethylprostaglandin E2↗

Elevated PGI2 and PGE2 production in the rat ileum following mild hypotension.

Ileal prostaglandin (PGs) biosynthesis was compared in female rats in normal mild hemorrhage (exposed to mild hypotension, reperfusion, and maintenance on hyperalimentation for 5 days) and control groups (instrumentation and hyperalimentation without hemorrhage). Tissue PG levels were analyzed by radiochromatographic analysis of microsomal membrane fractions prepared from the ileum in each group. Total cyclooxygenase activity in the normal and control groups was modest, with low levels of 6-keto-PGF1 alpha, PGE2, PGF2 alpha, thromboxane B2, PGA2, and PGD2 being produced. Hemorrhage, reperfusion, and maintenance on hyperalimentation for 5 days markedly induced total cyclooxygenase activity in the female rat ileum. Ileal microsomal membrane fractions obtained from the mild hemorrhage group synthesized levels of individual PGs three- to seven-fold higher than the normal or control groups, with 6-keto- PGF1 alpha (breakdown product of prostacyclin), PGE2, and PGA2 demonstrating the highest levels of biosynthesis. These data suggest that the gastrointestinal tract could serve as a source for the elevated PGs known to occur in various shock models.

Animals↗

Temporalis fascia grafts for facial and nasal contour augmentation.

For the past 70 years, fascial grafts have been used in reconstructive surgery mainly because of their tensile strength. Although the thigh (fasciae latae) has been the principal donor site, fascia taken from the temporalis muscle has the advantages of (1) ease of harvest under local anesthesia, (2) usually being in the same operative field, (3) minimal postoperative discomfort, and (4) negligible residual scar deformity. These grafts can be effectively used as the sole source of contour augmentation of facial depressions in primary as well as secondary rhinoplasty. Such grafts undergo an initial uniform shrinkage (approximately 20 percent) during the first 4 to 6 weeks postoperatively due to compaction and condensation of the fibrous tissue of the fascia, after which the grafts stabilize and become firm. Concavities should be overcorrected accordingly. No inflammation or encapsulation has been seen clinically or histologically in 18 patients followed for periods ranging from 6 to 18 months.

Adolescent↗