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Biomedical subjects

R Bartlett

Publications and source records attributed to R Bartlett.

At least 37 records · Page 2Linked to original sources

Surgical management of cutis aplasia with high-flow sinus pericranii.

Cutis aplasia (cutis aplasia congenita cystica) is a rare congenital disorder with failure of completion of the extracerebral coverings, involving a defect in the scalp and often a cranial defect. A case of cutis aplasia is reported with an associated high-flow venous fistula or sinus pericranii, resulting in altered venous drainage of sagittal sinus blood through dilated scalp veins. Radiological workup to ensure patency of the superior sagittal sinus was critical to the surgical management in this case.

Adult↗

Program for generation of three-dimensional finite element mesh from magnetic resonance imaging scans of human limbs.

A PC-AT based program for conversion of magnetic resonance imaging (MRI) scans into coordinate input for finite element mesh generation is presented. The program is written in Borland C+ +3.1 and is compatible with every general-use personal computer, permitting the use of MS-DOS 3.0 or higher with a Microsoft mouse. The program is menu driven and does not demand specialised knowledge from the user. The system and memory requirements are minimal--640 kB RAM--and it runs as a stand-alone program. A second program allows the construction of a three-dimensional representation of the limb sub-structure and generation of the FE mesh from the converted cross-sectional scans. The capabilities of the program are demonstrated using cross-sectional scans of the upper arm; the fat, muscle and bone contours were obtained to a very high level of precision (0.4 mm).

Arm↗

Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron's syndrome).

We have characterized the GH receptor mutation that is responsible for extreme short stature and GH insensitivity in a Bahamian genetic isolate. Heights of affected individuals ranged from -4.0 to -6.3 SD. Like others with Laron's syndrome, they had normal to high serum GH concentrations and low serum insulin-like growth factor I concentrations. Circulating levels of GH-binding protein activity were below limits of detection. Amplification of exons 2-7 and screening with single strand conformational polymorphism analysis located an abnormality in exon 7. Sequencing identified homozygosity for a C to T transition in the third position of codon 236. Reverse transcription and PCR amplification of complementary DNA from lymphocytes showed that this same sense mutation generated a new splice donor site 63 bp 5' to the normal exon 7 splice site. This novel site was used to the exclusion of the normal site in homozygotes. Both normal and variant messenger ribonucleic acid species were detected in heterozygotes. The predicted protein lacks 21 amino acids, including those defining the WS-like motif of the GH receptor extracellular domain. The high frequency of Laron's syndrome in this isolated island population probably reflects the introduction of the G236 splice mutation by a settler early in the 300-yr history of English settlement.

Adolescent↗

Inverse optimization: functional and physiological considerations related to the force-sharing problem.

This paper is a review of the optimization techniques used for the solution of the force-sharing problem in biomechanics; that is, the distribution of the net joint moment to the force generating structures such as muscles and ligaments. The solution to this problem is achieved by the minimization (or maximization) of an objective function that includes the design variable (usually muscle forces) that are subject to certain constraints, and it is generally related to physiological or mechanical properties such as muscle stress, maximum force or moment, activation level, etc. The usual constraints require the sum of the exerted moments to be equal to the net joint moment and certain boundary conditions restrict the force solutions within physiologically acceptable limits. Linear optimization (objective and constraint functions are both linear relationships) has limited capabilities for the solution of the force sharing problem, although the use of appropriate constraints and physiologically realistic boundary conditions can improve the solution and lead to reasonable and functionally acceptable muscle force predictions. Nonlinear optimization provides more physiologically acceptable results, especially when the criteria used are related to the dynamics of the movement (e.g., instantaneous maximum force derived from muscle modeling based on length and velocity histories). The evaluation of predicted forces can be performed using direct measurements of forces (usually in animals), relationship with EMG patterns, comparisons with forces obtained from optimized forward dynamics, and by evaluating the results using analytical solutions of the optimal problem to highlight muscle synergism for example. Global objective functions are more restricting compared to local ones that are related to the specific objective of the movement at its different phases (e.g., maximize speed or minimize pain). In complex dynamic activities multiobjective optimization is likely to produce more realistic results.

Biomechanical Phenomena↗

The relationship between basketball shooting kinematics, distance and playing position.

Three-dimensional cinematography (100 Hz) was used to establish the relationship between distance and the kinematics of shooting with respect to playing position in basketball. Fifteen subjects, divided into guards, forwards and centres (all n = 5), performed jump shots from each of three distances: 2.74, 4.57 and 6.40 m from the basket. Increases in mean release speed were found as shooting distance increased for all groups. This was due to increased angular velocities of both shoulder flexion and elbow extension and an increased speed of the centre of mass in the direction of the basket. Release angles for the two shorter distances (52-55 degrees) tended to provide the advantage of a steep angle of entry into the basket, whereas those at the longest distance (48-50 degrees) were closer to those requiring the minimum possible release speed. All groups exhibited an earlier timing of release as shooting distance increased, which gave rise to an earlier rotation of the shoulder axis. The more consistent changes in kinematic patterns with changes in shooting distance exhibited by guards as compared to centres would suggest that such adjustments are easier to make for those players who regularly shoot from long range.

Adult↗

Biomechanical factors critical for performance in the men's javelin throw.

In the men's javelin event the athlete throws an 800g implement into a 40 degrees sector. The objective is to throw as far as possible. Compared with most other throwing implements, the javelin is relatively aerodynamic. Even so, the most important release parameter is still the release speed. Maximising this parameter gives the athlete the best chance of attaining success in the event. For an elite thrower, as much as 70% of the release speed of the javelin is developed in the last 0.1 second. As such, the movements of throwers during this period and immediately preceding it have received attention from researchers. It would appear that a thrower's body position at the instant of final foot strike, his ability to transfer momentum between the lower body and the upper body during the delivery, and coordination of the working body segments in the most effective manner are linked to his success in the event. This paper reviews the most important biomechanical research on the men's javelin throw and highlights findings such as these which may improve the understanding of how elite javelin throwers achieve success.

Biomechanical Phenomena↗

The fission yeast gene pmt1+ encodes a DNA methyltransferase homologue.

DNA methylation of cytosine residues is a widespread phenomenon and has been implicated in a number of biological processes in both prokaryotes and eukaryotes. This methylation occurs at the 5-position of cytosine and is catalyzed by a distinct family of conserved enzymes, the cytosine-5 methyltransferases (m5C-MTases). We have cloned a fission yeast gene pmt1+ (pombe methyltransferase) which encodes a protein that shares significant homology with both prokaryotic and eukaryotic m5C-MTases. All 10 conserved domains found in these enzymes are present in the pmt1 protein. This is the first m5C-MTase homologue cloned from a fungal species. Its presence is surprising, given the inability to detect DNA methylation in yeasts. Haploid cells lacking the pmt1+ gene are viable, indicating that pmt1+ is not an essential gene. Purified, bacterially produced pmt1 protein does not possess obvious methyltransferase activity in vitro. Thus the biological significance of the m5C-MTase homologue in fission yeast is currently unclear.

Amino Acid Sequence↗

CD4+ cytolytic T cells can destroy autologous and MHC-matched macrophages but fail to kill intracellular Mycobacterium bovis-BCG.

Mycobacterium bovis-BCG infected macrophages were exposed in vitro to PPD-stimulated T lymphocytes from tuberculin responsive donors or to a panel of mycobacterial-antigen specific CD4+ T cell clones. Both polyclonal and clonal T cells caused considerable antigen-specific lysis of autologous or MHC class II matched macrophages. However, lysis of infected macrophages did not significantly affect the number of viable mycobacteria which were released into the culture media from lysed macrophages. In tuberculosis, CD4+ cytolytic T cells may be primarily involved in tissue destruction and lack a significant role in acquired cellular immunity.

CD4-Positive T-Lymphocytes↗

Inflammatory pseudotumour of the central nervous system: clinicopathological study of one case and review of the literature.

A 58-year-old male who had been diagnosed as having polymyositis was found to have a mass in the fourth ventricle. This mass showed features of an inflammatory pseudotumor. This lesion has been described in many parts of the body including the central nervous system. This case showed some features different from the previously reported cases in the central nervous system (i.e. presence of necrosis and association with polymyositis) which may throw some light on the pathogenesis of the condition. Inflammatory pseudotumour is most likely to be caused by an exaggerated immunological process and is sometimes associated with high levels of serum immunoglobulin.

Biopsy↗

Apoptosis in human skin development: morphogenesis, periderm, and stem cells.

During human skin development, embryonic- and fetal-specific periderm cells and incompletely keratinized cells are replaced by keratinocytes that differentiate while stratifying to form the fully functional epidermis. Proliferating basal cells of fetal skin also develop into epidermal appendages such as hair follicles and glands. We demonstrate that programmed cell death, not emphasized in conventional epidermal biology, has an important function in establishing the final architecture of the human epidermis and its appendages. Immunohistochemical localization of transglutaminases in fetal periderm, intermediate epidermal cells, and within appendages coincides with DNA fragmentation indicating that apoptosis is involved in deletion of these stage-specific cells and remodeling of appendages. The data also suggest that terminal differentiation of epidermal cells might be a specialized form of apoptosis. The pattern of expression of bcl-2, a gene associated with survival of some cells, is exclusive of the distribution patterns of markers of the cell death pathway. Bcl-2 protein is correlated with specific morphogenetic events in hair follicles and eccrine sweat glands, and its presence in single cells of the hair follicle bulge suggests that Bcl-2 may be a stem cell marker.

Adult↗

Two enzyme linked immunosorbent assays for detecting antibodies against meningococcal capsular polysaccharides A and C.

AIMS: To evaluate two of the recent methods of coating microtitre plates in the enzyme linked immunosorbent assay (ELISA) for detecting human antibodies against meningococcal capsular polysaccharides A and C with a view to validating a specific meningococcal antibody assay for routine clinical use. METHODS: Two four-layer ELISA protocols were standardised: one method utilised meningococcal polysaccharides conjugated to poly-L-lysine polypeptide for coating the microtitre plates; another used polysaccharides mixed with methylated human serum albumin (mHSA). Titration curves were plotted for the ELISAs and the squared Pearson correlation coefficient (R2) was used to determine the degree of accuracy of fit of the curves. Specificity tests were performed by inhibition and adsorption studies. RESULTS: Both methods gave good titration curves with a high R2 of > 0.98, indicating a high degree of accuracy in forming the curves. The titration end point after vaccination, obtained by the mHSA method, was 20 times higher, however, than that obtained by the poly-L-lysine method. Specificity tests showed that in the ELISA using polysaccharide/poly-L-lysine, antibody activity of a pre-vaccination serum sample was inhibited by 37%, and of post-vaccination serum by 50% with 1000-fold excess antigen. Antibody activity (post-vaccination) was reduced by 51% and 59%, respectively, by adsorption with antigen-coated Sepharose beads or adsorption with suspensions of killed meningococci. In contrast, antibody activity of a pre-vaccination serum was inhibited by 60% and a post-vaccination serum by 90% in ELISA employing polysaccharides mixed with mHSA. Reproducibility was better with the use of methylated human serum albumin than with poly-L-lysine; the former showed intrabatch and interbatch coefficients of variation of 4% and 2%, respectively, compared with 43% (intrabatch) and 16% (interbatch) obtained with the poly-L-lysine. CONCLUSION: It is concluded that the antibody assay using meningococcal polysaccharides groups A and C mixed with mHSA is much better than that using polysaccharides coupled with poly-L-lysine.

Antibodies, Bacterial↗

Beryllium-induced disturbances of the murine immune system reflect some phenomena observed in sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown origin. In respect to clinical and immunological characteristics, it is indistinguishable from berylliosis. As an approach to develop a murine model reflecting some aspects of sarcoidosis, we attempted to induce berylliosis in mice by treating inbred F1 mice (C57B16 x DBA/2) with 3 mg beryllium sulfate (BeSO4) per kg body weight intraperitoneally. Either pure BeSO4 or BeSO4 in combination with incomplete Freund's adjuvant was administered. Alternatively, pure BeSO4 was injected 2 days after a single application of cyclophosphamide (150 mg/kg). The spleen index, the spontaneous and phorbolmyristate acetate (PMA)-induced radical oxygen intermediates (ROI) released by peritoneal macrophages, and the proliferative activity of spleen mononuclear cells in response to BeSO4 and concanavalin A (ConA) were evaluated and compared to the corresponding changes observed in sarcoidosis. In all three modes of BeSO4 treatment, the spontaneous ROI release by peritoneal macrophages was significantly elevated. These elevations were very similar to those observed with alveolar macrophages in active sarcoid alveolitis. After BeSO4 treatment, a small proliferative activity of spleen mononuclear cells in response to BeSO4 could be observed. Further, BeSO4-treated spleen mononuclear cells exhibited a markedly reduced response to ConA stimulation (approximately 20% of control) which parallels the reduced proliferative capacity of sarcoid peripheral blood mononuclear cells (approximately 45% of control). This reduction could be abolished by pretreating the mice with cyclophosphamide. BeSO4 treatment in combination with incomplete Freund's adjuvant resulted in a significant increase of spleen mononuclear cell proliferation (1.9-fold) after in vitro stimulation with BeSO4, and prevented the low responsiveness to ConA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide.

The active metabolite of leflunomide, A77 1726 inhibits the proliferation of a variety of mammalian cell lines in culture. Epidermal growth factor (EGF)-dependent proliferation is inhibited by A77 1726 at an effective dose of 30-40 microM. A77 1726 appears to directly inhibit the EGF receptor tyrosine-specific kinase activity both in intact cells and purified EGF receptors at the same effective dose. These data suggest that leflunomide inhibits cellular proliferation by the inhibition of tyrosine-specific kinase activities.

Aniline Compounds↗

Safety assessment of high-dose narcotic analgesia for emergency department procedures.

STUDY OBJECTIVE: To evaluate the safety of high-dose IV narcotics in patients requiring analgesia for painful emergency department procedures. DESIGN: Prospective multicenter clinical trial. SETTING: Five adult urban EDs. METHODS AND MEASUREMENTS: All patients received IV meperidine (1.5 to 3.0 mg/kg) titrated to analgesia followed by a painful procedure. Vital signs and alertness scale were recorded at regular intervals, and patients were observed for four hours. Adverse events were monitored and documented. Comparisons between baseline and postanalgesia intervals were made with a repeated measures ANOVA (Dunnett's test). RESULTS: Although statistically significant changes in vital signs and alertness scale occurred, they were not clinically significant. Opiate reversal with naloxone was not needed in any patient, and no significant respiratory or circulatory compromise occurred. CONCLUSION: This study of 72 patients demonstrates that high-dose narcotic analgesia is appropriate, well tolerated, and safe when used in selected patients before painful procedures in the ED. Narcotic antagonists and resuscitation equipment nonetheless should be available to maximize safety.

Adolescent↗

Venovenous compares favorably with venoarterial access for extracorporeal membrane oxygenation in neonatal respiratory failure.

Traditional extracorporeal membrane oxygenation via the venoarterial route requires cannulation and ligation of the internal jugular vein and common carotid artery. Concerns about ligation of the common carotid artery prompted development of a 14F double-lumen internal jugular vein cannula for venovenous oxygenation for neonates with respiratory failure. We retrospectively compared 22 patients supported by venovenous bypass and 20 patients supported with traditional venoarterial bypass. The two groups of patients were selected to be comparable in terms of diagnosis and severity of respiratory insufficiency. The diagnoses in both groups were limited to meconium aspiration syndrome or persistent pulmonary hypertension of the newborn. The average oxygenation indexes in the two groups were similar (46.6 venovenous, 47.2 venoarterial, p = not significant). Venovenous access allowed flow rates of more than 100 ml/kg per minute, which were adequate for gas exchange support. One patient required conversion from venovenous to venoarterial bypass because of hemodynamic instability. The average time of bypass support was 115 hours (range 24 to 338 hours) for venovenous bypass and 134 hours (range 47 to 361 hours) for venoarterial bypass (p < 0.05). The time to extubation after decannulation from extracorporeal membrane oxygenation was 133 hours (range 38 to 720 hours) for venovenous support and 100 hours (range 27 to 192 hours) for venoarterial support (p = not significant). One patient supported with venoarterial bypass had an intracranial hemorrhage. There were no documented neurologic injuries in the patients managed with venovenous bypass. There were no deaths in either group. Venovenous extracorporeal membrane oxygenation through a double-lumen cannula can adequately provide respiratory support for neonates with pulmonary failure and effectively avoids ligation of the common carotid artery.

Carotid Artery, Common↗

Extracorporeal life support for adult cardiorespiratory failure.

BACKGROUND: Extracorporeal membrane oxygenation is routinely used for neonatal respiratory failure but is considered unsuccessful in adults based on old studies and old methods. We conducted a new phase 1 trial of modern extracorporeal life support (ECLS) in moribund adults with cardiorespiratory failure. METHODS: Criteria for initiation of ECLS were 90% mortality risk despite maximal conventional care, good potential for recovery, age < 60 years, and no contraindication to anticoagulation. Vascular access for ECLS was performed by operative or percutaneous cannulation. Continuous systemic heparinization was used, maintaining whole blood activated clotting time between 160 to 180 seconds. Blood components were transfused as necessary. Lung management included low rate and low pressure ventilation with an inspired oxygen fraction 0.5 or less. RESULTS: Forty patients were treated with ECLS, 30 with primary respiratory failure and 10 with primary cardiac failure. Twenty-two patients recovered lung or heart function, and 18 patients survived and were discharged from the hospital (14 with respiratory failure and four with cardiac failure, overall survival 45%). The major complication of ECLS was bleeding. CONCLUSIONS: With modern techniques, ECLS can be lifesaving in adult cardiorespiratory failure when conventional therapy has failed.

Adolescent↗