Computer simulation of the dynamics of a human arm and orthosis linkage mechanism

BACKGROUND: A prospective study was conducted to evaluate the clinical usefulness of three-dimensional (3D) surface-shaded maps for routine practice of myocardial perfusion single-photon emission computed tomography (SPECT) by comparison with 2D slices and 2D bull's-eye qualitative analysis. METHODS AND RESULTS: Angiograms were performed on 201 consecutive patients, 155 with coronary artery disease (CAD) and 46 with no significant CAD. One-day 201TI stress/rest-reinjection protocol was performed in 110 patients, and 1-day 99mTc-sestamibi or tetrofosmin stress/rest protocol was performed in 91. The stress protocol was either exercise or dipyridamole (0.56 mg/kg) infusion. Three-dimensional surface maps were obtained by using a threshold for the transaxial data at 50%, 55%, 60%, 65%, and 70% of the maximum pixel value in the first 60 patients. Interpretation of 3D maps was based on the presence of a complete (transmural-looking) perfusion hole within the myocardial wall; doubtful patterns were considered pathologic or normal. Good diagnostic values were found for the 50% to 60% thresholds, but the 60% setting showed the best concordance with multislice and bull's-eye analysis; higher values drastically degraded the specificity. Considering doubtful patterns as normal clarified interpretation and led to a small loss in sensitivity but high gain in specificity. Applied to the whole population, the 3D maps using a 60% threshold provided similar diagnostic value to detect CAD as did conventional and bull's-eye analysis. Moreover, the 3D maps showed a trend toward higher specificity and a proportionally smaller decrease in sensitivity (sensitivity: 92.9%, 90.3%, 89.7%; specificity: 45.6%, 50.0%, 58.7% for tomograms, bull's-eye analysis, and 3D maps, respectively), especially for the detection of left anterior descending and right CAD. Multivessel disease was detected in an identical manner. Three-dimensional maps might improve detection of perfusion defects in the basal regions. However, 3D maps were found to be less sensitive than slices and particularly bull's-eye analysis for the reversibility of stress defects. CONCLUSIONS: Three-dimensional surface display of myocardial perfusion is a valuable independent tool for determining presence, extent, and location of CAD. It can convey useful first-look information to the referring physician, especially through a cine-rotational motion (as done in our practice through use of a floppy disk.     

Seroprevalence of Borrelia burgdorferi in dogs in Alabama, USA

A random sample of private small-animal practices in Alabama submitted sera from dogs with known tick contact. A total of 579 samples from the three geographic regions of the state were collected (58% of the targeted sample size). Sera were screened for antibodies to Borrelia burgdorferi using an indirect fluorescent antibody (IFA) test which had a sensitivity and specificity of greater than 90%. Anti-B burgdorferi titers of > or = 1:64 were considered to be positive, based on results from B. burgdorferi-inoculated dogs. Ten of the 579 samples (1.7%) were positive, and titers ranged from 1:64 to 1:512. Seropositive dogs were found throughbout the state, and there was no significant difference in seroprevalence by region (Mantel-Haenszel chi 2, P = 0.85). These results indicate that the seroprevalence for canine Lyme disease in Alabama is low and that use of the canine Lyme disease vaccine is not justified.     

Long-term efficacy of total SILASTIC implants: a subjective analysis

A retrospective analysis of the long-term efficacy of total SILASTIC implant arthroplasty performed before 1986 is presented. A total of 50 patients responded to subjective questionnaires regarding pain, function, complications, and overall patient satisfaction. The average age of the patients at the time of surgery was 55.1 years with an average follow-up of 13.4 years (range 10.7 to 16.9 years). Ninety-seven percent of patients reported relief from pain, and the overall success rating was 90.7%. Results were calculated based on a modification of the American Orthopaedic Foot and Ankle Society clinical rating system; the mean rating was 87.3. Attention must be directed at realigning the joint via appropriate osteotomies and soft tissue balancing procedures for increased success. Although radiographic deterioration of the implant was demonstrated in all implants, this deterioration did not correlate with patient satisfaction and should not be the sole criterion for implant removal. We conclude that total implant arthroplasty is a proven procedure for long-term relief of pain in selected patients with degenerative joint disease of the first metatarsophalangeal joint.     

A comparison of resource costs for head and neck reconstruction with free and pectoralis major flaps

A series of 178 immediate reconstructions with regional or distant tissue for repair of oropharyngeal defects caused by treatment of head and neck cancer was reviewed to determine whether reconstruction with free flaps was more or less expensive than reconstruction with regional myocutaneous flaps. In this series, three types of flaps were used: the radial forearm free flap (n = 89), the rectus abdominis free flap (n = 56), and the pectoralis major myocutaneous flap (n = 33). Resource costs were determined by adding all costs to the institution of providing each service studied using salaried employees (including physicians). The two free-flap groups were combined to compare free flaps with the pectoralis major myocutaneous flap, a regional myocutaneous flap. Failure rates in the two groups were similar (3.0 percent for pectoralis major myocutaneous flap, 3.4 percent for free flaps). The mean costs of surgery were slightly higher for the free flaps, but the subsequent hospital stay costs were lower. Therefore, the total mean resource cost for the free-flap group ($28,460) was lower than the cost for the myocutaneous flap group ($40,992). The pectoralis major myocutaneous flap may have been selected for more patients with advanced disease and systemic medical problems, contributing to longer hospitalization and added cost. Nevertheless, this study suggests that free flaps are not more expensive than other methods and may provide cost savings for selected patients.     

Non-peptide glycoprotein IIb/IIIa inhibitors. 17. Design and synthesis of orally active, long-acting non-peptide fibrinogen receptor antagonists

The synthesis and pharmacological evaluation of 5 (L-738, 167), a potent, selective non-peptide fibrinogen receptor antagonist is reported. Compound 5 inhibited the aggregation of human gel-filtered platelets with an IC50 value of 8 nM and was found to be > 33000-fold less effective at inhibiting the attachment of human endothelial cells to fibrinogen, fibronectin, and vitronectin than it was at inhibiting platelet aggregation. Ex vivo platelet aggregation was inhibited by > 85% 24 h after the oral administration of 5 to dogs at 100 micrograms/kg. The extended pharmacodynamic profile exhibited by 5 appears to be a consequence of its high-affinity binding to GPIIb/IIIa on circulating platelets and suggests that 5 is suitable for once-a-day dosing.     

Dynamics of ATP-induced calcium signaling in single mouse thymocytes

Extracellular ATP (ATPo) elicits a robust change in the concentration of intracellular Ca2+ ([Ca2+]i) in fura-2-loaded mouse thymocytes. Most thymocytes (60%) exposed to ATPo exhibited a biphasic rise in [Ca2+]i; [Ca2+]i rose slowly at first to a mean value of 260 nM after 163 s and then increased rapidly to a peak level of 735 nM. In many cells, a declining plateau, which lasted for more than 10 min, followed the crest in [Ca2+]i. Experiments performed in the absence of extracellular [Ca2+]o abolished the rise in thymocyte [Ca2+]i, indicating that Ca2+ influx, rather than the release of stored Ca2+, is stimulated by ATPo. ATPo- mediated Ca2+ influx was potentiated as the [Mg2+]o was reduced, confirming that ATP4- is the active agonist form. In the absence of Mg2+o, 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) proved to be the most effective agonist of those tested. The rank order of potency for adenine nucleotides was BzATP4->ATP4->MgATP2->ADP3-, suggesting purinoreceptors of the P2X7/P2Z class mediate the ATPo response. Phenotyping experiments illustrate that both immature (CD4-CD8-, CD4+CD8+) and mature (CD4+CD8-, CD4-CD8+) thymocyte populations respond to ATP. Further separation of the double-positive population by size revealed that the ATPo-mediated [Ca2+]i response was much more pronounced in large (actively dividing) than in small (terminally differentiated) CD4+CD8+ thymocytes. We conclude that thymocytes vary in sensitivity to ATPo depending upon the degree of maturation and suggest that ATPo may be involved in processes that control cellular differentiation within the thymus.     

The effect of erythromycin on the CYP3A component of sertindole clearance in healthy volunteers

The effect of erythromycin on the pharmacokinetic disposition of oral sertindole, a new antipsychotic compound, was investigated. Ten subjects who completed the study received a single 4-mg dose of sertindole without or with concomitant erythromycin 250 mg taken orally 4 times daily. Coadministration of sertindole and erythromycin led to a 33% decrease (P < 0.05) in mean (+/- SD) time to reach maximum plasma concentration (tmax) value and a 15% elevation (P < 0.05) in the mean maximum plasma concentration (Cmax) value of sertindole. The mean area under the concentration-time curve (AUC) value of sertindole did not change significantly in the presence of erythromycin (alone: 159 +/- 111 ng.hr/mL, in combination: 179 +/- 144 ng.hr/mL, P > 0.05). The presence of erythromycin also significantly increased the dehydrosertindole Cmax and AUC means by 16% and 21%, respectively, possibly due to inhibition of the CYP3A metabolic isozyme responsible for the elimination of this metabolite. The rate of absorption of sertindole and the rate of appearance of dehydrosertindole in the systemic circulation after a 4-mg sertindole single dose were slightly enhanced by concomitant dosing of erythromycin. In conclusion, there is a small but noticeable effect of erythromycin on the pharmacokinetic disposition of sertindole. The effects are believed to have little clinical significance.     

Comparison of nipple projection with the modified double-opposing tab and star flaps

This study compared nipple projection after nipple reconstruction (following breast mound reconstruction) with either the modified double-opposing tab flap or the star flap. Areolar reconstruction and pigmentation of the nipple were achieved with tattooing. Nipple projection for 153 nipples was measured at least 6 months after the reconstruction, when projection was believed to have become stable. Mean follow-up was 2.27 years. In the 106 nipples reconstructed with modified double-opposing tab flaps, the mean projection was 2.4292 mm, while in the 47 nipples reconstructed with star flaps, the mean projection was 1.9681 mm (p = 0.021). We conclude that although both methods are effective, the modified double-opposing tab flap has slightly more projection after approximately 2 years. It is not known, however, whether this is because of reduced flap atrophy or longer initial projection by the modified double-opposing tab flap; further studies are ongoing.     

Comparative mapping of Andropogoneae: Saccharum L. (sugarcane) and its relation to sorghum and maize

Comparative genetic maps of Papuan Saccharum officinarum L. (2n = 80) and S. robustum (2n = 80) were constructed by using single-dose DNA markers (SDMs). SDM-framework maps of S. officinarum and S. robustum were compared with genetic maps of sorghum and maize by way of anchor restriction fragment length polymorphism probes. The resulting comparisons showed striking colinearity between the sorghum and Saccharum genomes. There were no differences in marker order between S. officinarum and sorghum. Furthermore, there were no alterations in SDM order between S. officinarum and S. robustum. The S. officinarum and S. robustum maps also were compared with the map of the polysomic octoploid S. spontaneum 'SES 208' (2n = 64, x = 8), thus permitting relations to homology groups ("chromosomes") of S. spontaneum to be studied. Investigation of transmission genetics in S. officinarum and S. robustum confirmed preliminary results that showed incomplete polysomy in these species. Because of incomplete polysomy, multiple-dose markers could not be mapped for lack of a genetic model for their segregation. To coalesce S. officinarum and S. robustum linkage groups into homology groups (composed of homologous pairing partners), they were compared with sorghum (2n = 20), which functioned as a synthetic diploid. Groupings suggested by comparative mapping were found to be highly concordant with groupings based on highly polymorphic restriction fragment length polymorphism probes detecting multiple SDMs. The resulting comparative maps serve as bridges to allow information from one Andropogoneae to be used by another, for breeding, ecology, evolution, and molecular biology.     

Transcobalamin II and in vitro proliferation of leukemic cells

Expression and stability of immunoglobulins in transgenic plants have been investigated and optimized by accumulation in different cellular compartments as cytosol, apoplastic space and endoplasmic reticulum (ER) as will be discussed in this review. In several cases described the highest accumulation of complete active antibodies was achieved by targeting into the apoplastic space. High-level expression of active recombinant single-chain Fv antibodies (scFv's) was obtained by retention of these proteins in the lumen of the endoplasmic reticulum. This has been shown for leaves and seeds of transgenic tobacco as well as for potato tubers. Transgenic tobacco seeds, potato tubers and tobacco leaves can facilitate stable storage of scFv's accumulated in the ER over an extended (seeds, tubers) or a short (leaves) period of time. The expression of specific scFv's in different plant species, plant organs and cellular compartments offers the possibility of blocking regulatory factors or pathogens specifically. Examples are scFv's expressed in the cytosol and the apoplastic space of transgenic plant cells modulating the infection process of plant viruses and a cytosolically expressed scFv that influenced the activity of phytochrome A protein. The immunomodulation approach has been shown to be also applicable for investigating the action of the phyto-hormone abscisic acid (ABA). High-level accumulation of specific anti-ABA scFv's in the ER of all leaf cells has been used to block the influence of ABA on the stomatal functions. Seed-specific expression of high amounts of anti-ABA-scFv's at a defined time of seed-development induced a developmental switch from seed ripening to vegetative growth. It has been demonstrated that ER retention is essential for the accumulation of sufficient scFv to bind high concentrations of ABA in the transgenic seeds.