Biomedical subjects
Publications and source records attributed to T Coyle.
Handlebar type injuries are well documented in the paediatric population. We describe a case complicated by a biloma, which was successfully treated with percutaneous drainage, guided radiologically. The imaging findings including CT, MRI and nuclear medicine techniques are presented.
During lateral leg raising, a synergistic inclination of the supporting leg and trunk in the opposite direction to the leg movement is performed in order to preserve equilibrium. As first hypothesized by Pagano and Turvey (J Exp Psychol Hum Percept Perform, 1995, 21:1070-1087), the perception of limb orientation could be based on the orientation of the limb's inertia tensor. The purpose of this study was thus to explore whether the final upper body orientation (trunk inclination relative to vertical) depends on changes in the trunk inertia tensor. We imposed a loading condition, with total mass of 4 kg added to the subject's trunk in either a symmetrical or asymmetrical configuration. This changed the orientation of the trunk inertia tensor while keeping the total trunk mass constant. In order to separate any effects of the inertia tensor from the effects of gravitational torque, the experiment was carried out in normo- and microgravity. The results indicated that in normogravity the same final upper body orientation was maintained irrespective of the loading condition. In microgravity, regardless of loading conditions the same (but different from the normogravity) orientation of the upper body was achieved through different joint organizations: two joints (the hip and ankle joints of the supporting leg) in the asymmetrical loading condition, and one (hip) in the symmetrical loading condition. In order to determine whether the different orientations of the inertia tensor were perceived during the movement, the interjoint coordination was quantified by performing a principal components analysis (PCA) on the supporting and moving hips and on the supporting ankle joints. It was expected that different loading conditions would modify the principal component of the PCA. In normogravity, asymmetrical loading decreased the coupling between joints, while in microgravity a strong coupling was preserved whatever the loading condition. It was concluded that the trunk inertia tensor did not play a role during the lateral leg raising task because in spite of the absence of gravitational torque the final upper body orientation and the interjoint coupling were not influenced.
We investigated the behavioral dynamics of human breathing-wrist movement coordination in a 1:1 frequency locking task. A pronation-supination wrist movement and a short trial duration were chosen to limit both mechanical and metabolic constraints on the respiratory system. Subjects voluntarily controlled their breathing rhythm to follow the metronome. We found that pronation-expiration and pronation-inspiration patterns coexisted as the (sole) stable fixed-point attractors of the coordination system. The pronation-expiration pattern was more stable than the pronation-inspiration pattern. Depending on the oscillation frequency, this differential stability gave rise to both absolute and relative coordination. These results show that simple behavioral laws of coordination encapsulate neural coupling dynamics evidenced from experimental research in human beings and animals. They challenge the classical view that such a coupling is not present for all imposed movement frequencies. Rather, relative coordination emerges as a result of the modification of coupling strength with frequency. These results can be accommodated by the asymmetric version of the HKB model of coordination dynamics. Thus, our data suggest that the principles and models of coordination dynamics may be taken as a reference to study the coupling of the motor and physiological subsystems involved in breathing-movement coordination.
Human CD150 (SLAM) is a glycoprotein expressed on the surface of T, B, natural killer, and dendritic cells. The extracellular domain of CD150 is the receptor for measles virus and CD150 acts as a co-activator on T and B cells. We characterized the mouse and human CD150 genes, each of which comprises seven exons spanning approximately 32 kb. Mouse CD150 mRNA was detected in T cells and in most thymocyte subsets, except CD4-8- cells. Surprisingly, the CD4-8- thymocytes of CD3gammadeltanull mice, but not of Ragnull or severe combined immunodeficiency mice, expressed CD150. Whereas high levels of CD150 were found in Th1 cells, only small amounts were detectable in Th2 cells. CD150 expression was up-regulated upon in vitro activation of mouse T cells by anti-CD3. The complete mouse CD150 gene is highly homologous to its human orthologue in terms of nucleotide sequences and intron/exon organization. The human genomic sequences indicate that all isoforms detected so far have arisen from alternative splicing events. As judged by fluorescence in situ hybridization, mouse CD150 mapped to Chromosome (Chr) 1, band 1H2.2-2.3, and human CD150 was found on Chr 1q22. Human and mouse CD150 share sequence homologies with six other genes, five of which - CD84, CD229 (Ly-9), CD244 (2B4), CD48, and 19A - are localized in a 250-kb segment in close proximity to the human gene. Their location and their sequence similarities strongly suggest that the CD150 family of cell surface receptors arose via successive duplications of a common ancestral gene.
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Gossypol, a polyphenolic compound which depletes cellular energy by inhibition of several intracellular dehydrogenases, has been shown to have antiproliferative activity against human glial tumor cell lines in vitro and in nude mouse xenografts. Human trials of gossypol as a male contraceptive have demonstrated safety of long-term administration. We studied the activity of Gossypol 10 mg PO bid in 27 patients with pathologically confirmed glial tumors which had recurred after radiation therapy. Fifteen patients had glioblastoma, 11 patients anaplastic astrocytoma, 1 patient relapsed low grade glioma. Response was assessed every 8 weeks using CT/MRI scan and clinical criteria including decadron requirement. Treatment was continued until disease progression. Two patients had partial response (PR); 4 had stable disease for 8 weeks or more. One patient maintained a PR with improved KPS for 78 weeks. The other had a PR lasting 8 weeks. Toxicity was mild: 2 heavily pretreated patients had mild thrombocytopenia, 5 patients developed hypokalemia, 3 patients developed grade 2 hepatic toxicity and peripheral edema. Gossypol levels measured by HPLC did not correlate with response or toxicity in this study. We conclude that gossypol is well tolerated and has a low, but measurable, response rate in a heavily pretreated, poor-prognosis group of patients with recurrent glioma. The presumed novel mechanism of action, lack of significant myelosuppression, and activity in patients with advance glioma support further study of gossypol as an antineoplastic agent.
In biological systems, obviously dissipative, some injection of muscle force is required in order to sustain rhythmic movement. As the movement frequency increases, the way the muscle-force-to-movement relationship evolves (in timing and amplitude) can be used to characterize some fundamental control properties, including whether the observed system is autonomous or forced. In the case of a simple rhythmic, biological movement (single-joint horizontal forearm movement), this question can be addressed by assuming that the processed electromyographic activity (EMG) is related to the muscle torques. In this case, 2 interesting phenomena can be observed as the frequency increases. The first is that the phase lag between the force and movement remains constant (40 degrees), and the second is that the co-contraction of the agonist and antagonist muscle groups increases with the square of the frequency. These results showed that the contribution of muscle forces to movement organization cannot be regarded in terms of an escapement in an autonomous system, nor in terms of a forcing function in a forced system.
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Gossypol is a lipid soluble polyphenolic compound isolated from cotton seed oil which has been previously shown to have antiproliferative activity in vitro against a variety of human solid tumor cell lines. It has been extensively tested in clinical trials as a male contraceptive agent and found to be well tolerated. Its mechanism of action is thought to be inhibition of cellular energy metabolism. It inhibits glycolysis through inhibition of LDH isoenzyme type 5, and it inhibits mitochondrial oxidative phosphorylation and electron transport. We tested the in vitro antiproliferative effect of gossypol against four well characterized human glioma cell lines, HS 683, U373, U87 and U138, and one rat glioma cell line, C6, using the colorimetric Microculture Tetrazolium Assay (MTT). Cytotoxicity was found to be concentration and time dependent and increased with incubation times up to 8 days. The relative sensitivity of the glioma cell lines to gossypol at 48 hour incubation correlated with their respective LDH isoenzyme profiles, with the more sensitive cell lines expressing increased cathodal LDH isoenzymes (LDH5). The in vitro cytotoxicity of gossypol to these CNS tumor lines was compared to the other non central nervous system solid tumor cell lines which had been previously reported as being sensitive to gossypol, including SW-13 (adrenal), MCF-7 (breast), T47-D (breast), and HeLa (cervical). Additional lines tested included SK-MEL-3 (melanoma), Colo 201 (colon) and BRW, a line established in our laboratory from a patient with a Primitive Neuroectodermal tumor. C6, HS 683, and BRW had similar IC50s as the sensitive solid tumor cell lines. U373, U87 and U138 had significantly less sensitivity at 48 hours. There was greater cytotoxicity and no significant differences in the IC50s between any of cell lines at 8 day incubations. Additionally, we tested the cytotoxicity of gossypol against BRW in vivo, using the nude mouse xenograft model. Gossypol, given at a dose of 30 mg/kg per day five days a week for four weeks orally via gavage, was found to decrease the mean tumor weight of treated xenografts by more than 50% as compared to untreated xenografts. These findings suggest that gossypol has potential for further study as an agent for the treatment of primary CNS malignancies.
The etiology of LGL leukemia is not known; however, we recently detected HTLV-II in a patient with LGL leukemia. In this study, we found that sera from 6 of 28 patients with LGL leukemia were positive for HTLV-I/II using a whole virus ELISA; moreover, the ELISA-negative sera were near the positive cut-off value. Therefore, we performed additional studies on these sera using commercially available assays which can confirm and distinguish HTLV-I from HTLV-II infection. Serum from only one patient was confirmed positive using conventional criteria (HTLV-II+). Sera from 25 patients (89%) had indeterminate reactivity on Western blot assays. Of these, sera from 21 (84%) reacted to gag protein p24; 12 (48%) reacted with recombinant env protein p21e, and 10 (40%) reacted with both. We could not detect HTLV-I/II pol or pX gene sequences in these patients using polymerase chain reaction analyses, with the exception of the HTLV-II-infected patient described previously. These data show that most patients with LGL leukemia are not infected with prototypical HTLV-I or HTLV-II. The frequent reactivity of patient sera to HTLV-I/II gag protein p24 and to env protein p21e, however, suggests that a deleted or variant form of HTLV-I/II may be associated with LGL leukemia.
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Needs assessments are essential for policy formulation and the appropriate design of intervention programs. Recent nationwide data show that among large metropolitan areas of the United States, Baltimore has one of the highest infant mortality rates and ranks in the worst top 10 for blacks and the top 5 for whites for most indicators of poor pregnancy outcome. In this paper, we present the methods and results of a needs assessment that used multiple sources of routinely collected data and was conducted for the purpose of identifying intervention factors contributing to infant mortality in Baltimore City. This needs assessment was used by the Baltimore City Health Department to successfully secure funding for the federal Healthy Start Infant Mortality Prevention Initiative. We present the results of the analyses, along with some of the proposed interventions that resulted from the needs assessment. We also discuss the limitations of this type of needs assessment as well as suggestions for future needs assessments for the design of interventions to improve perinatal health.
We studied a patient with large granular lymphocyte (LGL) leukemia for evidence of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient was positive for HTLV-I/II antibodies by enzyme-linked immunosorbent assay (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation assays. Results of a synthetic peptide-based ELISA showed that the seropositivity was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic amplification of DNA from bone marrow sections using the polymerase chain reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene sequences. Cloning and sequencing of amplified products showed that the HTLV-II pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV-II isolates examined in our laboratory. HTLV infection may have a role in some patients in the pathogenesis of LGL leukemia.
The authors report the clinical features of hypersensitivity reactions believed to result from procarbazine in eight patients treated with mechlorethamine, vincristine, and procarbazine (MOP) for high-grade glioma. There was one instance of hypersensitivity in 7 patients treated for recurrent disease and seven instances in 16 patients treated with an adjuvant protocol using MOP directly after surgery. Maculopapular rash was seen in seven of eight, fever was seen in four of eight, and reversible abnormal liver function test results were seen in three of four patients. Pulmonary toxic effects were seen in five of eight patients and consisted of isolated interstitial pneumonitis in one, fever and infiltrate after rechallenge with procarbazine after previous rash in two, and cough accompanying rash in two. The toxic effects were mild to moderate in six patients but severe to life threatening in the two who were rechallenged after development of rash. The observed incidence of rash during adjuvant therapy was higher than that previously found by the authors for recurrent disease, and it appears to be higher than has been reported in Hodgkin's disease, lymphoma, and other solid tumors. The findings by the authors suggest that a high index of suspicion be kept for hypersensitivity reactions to procarbazine when treating primary brain tumors and that, contrary to the experience in other settings, procarbazine be stopped if rash develops.
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Allelic variants of kappa-casein and beta-lactoglobulin were used to estimate chromosome substitution effects on transmitting abilities for yield traits among sons of two Holstein sires. Sire 1 was a heterozygote for both loci, whereas sire 2 was a heterozygote for beta-lactoglobulin only. Transmitting abilities for fat percentage and the exchange of protein and fat (protein yield minus fat yield) were influenced by kappa-casein genotype among offspring of sire 1. The B allele of kappa-casein was associated with a decrease in fat percentage, whereas fat yield was not affected; the result was 4.5 kg more transmitting ability for protein than for fat. Favorable chromosome substitution effects on transmitting abilities for fat percentage, protein yield, and the exchange of protein and fat were also observed for the A allele of beta-lactoglobulin among offspring of sire 1; there were consistent but not significant estimates for sire 2. These results suggest that different estimates could be obtained from offspring of different parents, perhaps from linkage disequilibrium between families. The chromosome substitution effects appeared to be in the direction opposite to the average correlation of milk fat and protein content; marker-assisted selection for increased yield of protein would result in decreased fat yield.
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We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma.