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Biomedical subjects

D B Smith

Publications and source records attributed to D B Smith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Esophageal dilation for endosonographic evaluation of malignant esophageal strictures is safe and effective.

OBJECTIVE: Endoscopic ultrasound (EUS) is accepted as the most accurate modality for T- and N-staging of esophageal cancer, but some malignant strictures prevent passage of the echoendoscope beyond the level of the tumor. This incomplete evaluation may decrease staging accuracy. Previous studies have yielded conflicting results regarding the safety and efficacy of esophageal dilation for EUS. METHODS: We prospectively evaluated 267 consecutive patients undergoing EUS for esophageal carcinoma staging at our institution over a 66-month period to determine the number of patients requiring dilation for EUS examination, the success of dilation, safety of dilation, and clinical importance. RESULTS: Among 267 endosonographic examinations of the esophagus, 81 (30.3%) required dilation to advance the echoendoscope beyond the level of the stricture. After dilation was performed, the echoendoscope could be passed through the stricture in 69 patients (85.2%), and in 63 of 67 of the patients dilated to > or = 14 mm (94.0%). No complications have occurred secondary to the dilations performed to permit completion of the endosonographic examination. Tumor staging by EUS after dilation was T2 (14.8%), T3 (56.8%), and T4 (21.0%), nodal staging N0 (14.6%) and N1 (75.3%); and M1 (9.9%). CONCLUSIONS: We conclude that incremental, stepwise dilation of malignant strictures to 14 mm is safe and effective in permitting echoendoscope passage beyond the stenosis. The presence of a malignant stricture does not seem to diminish the utility of EUS staging of esophageal cancer.

Catheterization↗
PubMed2000

Surface geometric analysis of anatomic structures using biquintic finite element interpolation.

The surface geometry of anatomic structures can have a direct impact upon their mechanical behavior in health and disease. Thus, mechanical analysis requires the accurate quantification of three-dimensional in vivo surface geometry. We present a fully generalized surface fitting method for surface geometric analysis that uses finite element based hermite biquintic polynomial interpolation functions. The method generates a contiguous surface of C2 continuity, allowing computation of the finite strain and curvature tensors over the entire surface with respect to a single in-surface coordinate system. The Sobolev norm, which restricts element length and curvature, was utilized to stabilize the interpolating polynomial at boundaries and in regions of sparse data. A major advantage of the current method is its ability to fully quantify surface deformation from an unstructured grid of data points using a single interpolation scheme. The method was validated by computing both the principal curvature distributions for phantoms of known curvatures and the principal stretch and principal change of curvature distributions for a synthetic spherical patch warping into an ellipsoidal shape. To demonstrate the applicability to biomedical problems, the method was applied to quantify surface curvatures of an abdominal aortic aneurysm and the principal strains and change of curvatures of a deforming bioprosthetic heart valve leaflet. The method proved accurate for the computation of surface curvatures, as well as for strains and curvature change for a surface undergoing large deformations.

Animals↗
PubMed2000

Hepatocyte growth factor is elevated in chronic lung injury and inhibits surfactant metabolism.

Adult respiratory distress syndrome may incorporate in its pathogenesis the hyperplastic proliferation of alveolar epithelial type II cells and derangement in synthesis of pulmonary surfactant. Previous studies have demonstrated that hepatocyte growth factor (HGF) in the presence of serum is a potential mitogen for adult type II cells (R. J. Panos, J. S. Rubin, S. A. Aaronson, and R. J. Mason. J. Clin. Invest. 92: 969-977, 1993) and that it is produced by fetal mesenchymal lung cells (J. S. Rubin, A. M.-L. Chan, D. P. Botarro, W. H. Burgess, W. G. Taylor, A. C. Cech, D. W. Hirschfield, J. Wong, T. Miki, P. W. Finch, and S. A. Aaronson. Proc. Natl. Acad. Sci. USA 88: 415-419, 1991). In these studies, we expand on this possible involvement of HGF in chronic lung injury by showing the following. First, normal adult lung fibroblasts transcribe only small amounts of HGF mRNA, but the steady-state levels of this message rise substantially in lung fibroblasts obtained from animals exposed to oxidative stress. Second, inflammatory cytokines produced early in the injury stimulate the transcription of HGF in isolated fibroblasts, providing a plausible mechanism for the increased amounts of HGF seen in vivo. Third, HGF is capable of significantly inhibiting the synthesis and secretion of the phosphatidylcholines of pulmonary surfactant. Fourth, HGF inhibits the rate-limiting enzyme in de novo phosphatidylcholine synthesis, CTP:choline-phosphate cytidylyltransferase (EC 2.7.7.15). Our data indicate that fibroblast-derived HGF could be partially responsible for the changes in surfactant dysfunction seen in adult respiratory distress syndrome, including the decreases seen in surfactant phosphatidylcholines.

Animals↗
PubMed2000

Functional motor unit failure precedes neuromuscular degeneration in canine motor neuron disease.

Hereditary canine spinal muscular atrophy (HCSMA) features rapidly progressive muscle weakness that affects muscles in an apparent proximal-to-distal gradient. In the medial gastrocnemius (MG) muscle of homozygous HCSMA animals, motor unit tetanic failure is apparent before the appearance of muscle weakness and appears to be presynaptic in origin. We determined whether structural changes in neuromuscular junctions or muscle fibers were apparent at times when tetanic failure is prevalent. We were surprised to observe that, at ages when motor unit tetanic failure is common, the structure of neuromuscular junctions and the appearance of muscle fibers in the MG muscle were indistinguishable from those of symptom-free animals. In contrast, in more proximal muscles, many neuromuscular junctions were disassembled, with some postsynaptic specializations only partially occupied by motor nerve terminals, and muscle fiber atrophy and degeneration were also apparent. These observations suggest that the motor unit tetanic failure observed in the MG muscle in homozygous animals is not due to synaptic degeneration or to pathological processes that affect muscle fibers directly. Together with previous physiological analyses, our results suggest that motor unit failure is due to failure of neuromuscular synaptic transmission that precedes nerve or muscle degeneration.

Animals↗
PubMed1999

A new variant of GB virus C/hepatitis G virus (GBV-C/HGV) from South Africa.

Phylogenetic analysis of the 5' non-coding region (5'NCR) sequences has demonstrated that GB virus C/hepatitis G virus (GBV-C/HGV) can be separated into three major groups that correlate with the geographic origin of the isolate. Sequence analysis of the 5'NCR of 54 GBV-C/HGV isolates from 31 blood donors, 11 haemodialysis patients and 12 patients with chronic liver disease suggests the presence of a new variant of GBV-C/HGV in the province of KwaZulu Natal, South Africa. Eleven isolates grouped as group 1 variants (bootstrap support, 90%) found predominantly in West and Central Africa, a further six isolates grouped as group 2 variants (bootstrap support, 58%) found in Europe and North America; five of which grouped as 2a (bootstrap support, 91%) and one as 2b (bootstrap support, 87%), the latter also includes isolates from Japan, East Africa and Pakistan. Although the remaining 37 GBV-C/HGV isolates were more closely related to group 1 variants (bootstrap support, 90%), they formed a cluster, which was distinct from all other known GBV-C/HGV sequences. None of the South African isolates grouped with group 3 variants described from Southeast Asia. Three variants of GBV-C/HGV exist in KwaZulu Natal: groups 1, 2 and a new variant, which is distinct from other African isolates.

Base Sequence↗
PubMed1999

MMG and EMG responses of the superficial quadriceps femoris muscles.

Eighteen adults performed isometric muscle actions of the leg extensors at 25, 50, 75, and 100% maximal voluntary contraction (%MVC) at leg flexion angles of 25, 50, and 75 degrees. The results indicated that isometric torque production increased as leg flexion angle increased (75 degrees > 50 degrees > 25 degrees). For each muscle tested (rectus femoris, vastus lateralis, and vastus medialis), the EMG amplitude increased up to 100%MVC at each leg flexion angle (25, 50, and 75 degrees). The MMG amplitude for each muscle, however, increased up to 100%MVC at 25 and 50 degrees of leg flexion, but plateaued from 75 to 100%MVC at 75 degrees of leg flexion. We hypothesize that the varied patterns for the MMG amplitude-isometric torque relationships were due to leg flexion angle differences in: (1) muscle stiffness, (2) intramuscular fluid pressure, or (3) motor unit firing frequency.

Adult↗
PubMed1999

Evolution of the hypervariable region of hepatitis C virus.

Despite being the most intensively studied part of the hepatitis C virus genome, our understanding of the function of the hypervariable region (HVR) at the NH2-terminus of the E2 protein remains very limited. During chronic infection the HVR usually changes over time, with changes usually mirrored by those of HVR-specific antibodies. Evidence is presented suggesting that the HVR is subject to constraint in its length, amino acid composition, and in the amino acid replacements that are tolerated at different positions. These constraints, and the pattern of HVR variation during chronic infection, suggest that it has an important role in virus infection. A causal relationship between HVR variation and persistence of HCV remains to be demonstrated.

Amino Acid Sequence↗
PubMed1999

Variation of hepatitis C virus following serial transmission: multiple mechanisms of diversification of the hypervariable region and evidence for convergent genome evolution.

We have studied the evolution of hepatitis C virus (HCV) from a common source following serial transmission from contaminated batches of anti-D immunoglobulin. Six secondary recipients were each infected with virus from identifiable primary recipients of HCV-contaminated anti-D immunoglobulin. Phylogenetic analysis of virus E1/E2 gene sequences [including the hypervariable region (HVR)] and part of NS5B confirmed their common origin, but failed to reproduce the known epidemiological relationships between pairs of viruses, probably because of the frequent occurrence of convergent substitutions at both synonymous and nonsynonymous sites. There was no evidence that the rate at which the HCV genome evolves is affected by transmission events. Three different mechanisms appear to have been involved in generating variation of the hypervariable region; nucleotide substitution, insertion/deletion of nucleotide triplets at the E1/E2 boundary and insertion of a duplicated segment replacing almost the entire HVR. These observations have important implications for the phylogenetic analysis of HCV sequences from epidemiologically linked isolates.

Adolescent↗
PubMed1999

Sequence diversity of TT virus in geographically dispersed human populations.

TT virus (TTV) is a newly discovered DNA virus originally classified as a member of the Parvoviridae. TTV is transmitted by blood transfusion where it has been reported to be associated with mild post-transfusion hepatitis. TTV can cause persistent infection, and is widely distributed geographically; we recently reported extremely high prevalences of viraemia in individuals living in tropical countries (e.g. 74% in Papua New Guinea, 83% in Gambia; Prescott & Simmonds, New England Journal of Medicine 339, 776, 1998). In the current study we have compared nucleotide sequences from the N22 region of TTV (222 bases) detected in eight widely dispersed human populations. Some variants of TTV, previously classified as genotypes 1a, 1b and 2, were widely distributed throughout the world, while others, such as a novel subtype of type 1 in Papua New Guinea, were confined to a single geographical area. Five of the 122 sequences obtained in this study (from Gambia, Nigeria, Papua New Guinea, Brazil and Ecuador) could not be classified as types 1, 2 or 3, with the variant from Brazil displaying only 46-50% nucleotide (32-35% amino acid) sequence similarity to other variants. This study provides an indication of the extreme sequence diversity of TTV, a characteristic which is untypical of parvoviruses.

Africa, Western↗
PubMed1999

Structural constraints on RNA virus evolution.

The recently discovered hepatitis G virus (HGV) or GB virus C (GBV-C) is widely distributed in human populations, and homologues such as HGV/GBV-CCPZ and GBV-A are found in a variety of different primate species. Both epidemiological and phylogenetic analyses support the hypothesis that GB viruses coevolved with their primate hosts, although their degree of sequence similarity appears incompatible with the high rate of sequence change of HGV/GBV-C over short observation periods. Comparison of complete coding sequences (8,500 bases) of different genotypes of HGV/GBV-C showed an excess of invariant synonymous sites (at 23% of all codons) compared with the frequency expected by chance (10%). To investigate the hypothesis that RNA secondary-structure formation through internal base pairing limited sequence variability at these sites, an algorithm was developed to detect covariant sites among HGV/GBV-C sequences of different genotypes. At least 35 covariant sites that were spatially associated with potential stem-loop structures were detected, whose positions correlated with positions in the genome that showed reductions in synonymous variability. Although the functional roles of the predicted secondary structures remain unclear, the restriction of sequence change imposed by secondary-structure formation provides a mechanism for differences in net rate of accumulation of nucleotide substitutions at different sites. However, the resulting disparity between short- and long-term rates of sequence change of HGV/GBV-C violates the assumptions of the "molecular clock." This places a major restriction on the use of nucleotide or amino acid sequence comparisons to calculate times of divergence of other viruses evolving under the same structural constraints as GB viruses.

Base Sequence↗
PubMed1999

A second outbreak of hepatitis C virus infection from anti-D immunoglobulin in Ireland.

OBJECTIVE: To investigate the infectivity for hepatitis C virus (HCV) of intravenous anti-D immunoglobulin batches manufactured in Ireland between 1991 and 1994. METHODS: Women who had received anti-D manufactured between 1991 and 1994 were screened for serological markers of HCV infection and for the presence of HCV RNA by RT-PCR amplification and virus genotyping. RESULTS: 44 women exposed to anti-D manufactured between 1991 and 1994 were polymerase chain reaction positive for HCV RNA, 19 of whom were infected with genotype 3a virus shown by phylogenetic analysis of the NS5B gene to be closely related to that from the single implicated donor. CONCLUSIONS: Anti-D manufactured in 1991-1994 transmitted infection of HCV genotype 3a. The prevalence of HCV-specific antibody in anti-D recipients was relatively low (0.59%), consistent with the low level of virus RNA in these anti-D batches.

Disease Outbreaks↗
PubMed1999

Fatigue-induced changes in bioprosthetic heart valve three-dimensional geometry and the relation to tissue damage.

BACKGROUND AND AIM OF THE STUDY: In a previous study, we used magnetic resonance (MR) imaging to reconstruct, three-dimensionally, porcine bioprosthetic heart valve (PBHV) cusp geometry. Initial results using three valves indicated that accelerated testing induced changes in cuspal shape, including focal regions of high curvature. Since for thin-walled shell structures, such as the PBHV cusp, curvature changes can affect the stress distribution independently from changes to mechanical properties, shape changes might have adverse effects on PBHV durability. METHODS: The MR technique was applied to an expanded valve database to explore more fully shape change with fatigue. The spatial curvature distribution was compared across valves subjected to a range of accelerated test times. RESULTS: Results confirmed our initial findings that PBHV cusps undergo a continuous, non-recoverable deformation with accelerated testing. This deformation resulted in an increase in the portion of cuspal surface exhibiting high curvature values. In one cusp we mapped structural information obtained by small-angle light scattering back to the three-dimensional cuspal surface using an interpolation technique. Results from the mapped cusp demonstrated a strong spatial correlation between elevated curvatures and structural damage. CONCLUSIONS: The observed changes in cuspal shape accelerate PBHV damage due to an increase in flexural strains induced by an increase in curvature reversal during operation, rather than an increase in tension during closure.

Bioprosthesis↗
PubMed1999

Mean power frequency and amplitude of the mechanomyographic signal during maximal eccentric isokinetic muscle actions.

The purpose of the present investigation was to examine the effects of knee angular velocity on the mean power frequency (MPF) and amplitude of the mechanomyographic (MMG) signal during maximal eccentric (ECC) isokinetic muscle actions. Eleven adult subjects performed maximal ECC muscle actions of the leg extensors on a calibrated Cybex 6000 dynamometer at knee angular velocities of 60, 120, and 180 degrees.s-1. MMG was detected by a piezoelectric crystal contact sensor placed over the vastus lateralis muscle. There were no significant (p > 0.05) velocity-related changes in ECC peak torque (PT) or MMG MPF, however, the mean MMG amplitude value at 60 degrees.s-1 was significantly less (p < 0.05) than that at 180 degrees.s-1. These results did not support our previous hypothesis that the velocity-related increase in MMG amplitude for maximal ECC isokinetic muscle actions was due to selective recruitment of fast twitch fibers and derecruitment of slow twitch fibers with increasing velocity.

Adult↗
PubMed1999

Urinary continence issues in oncology.

Urinary incontinence may occur with many types of cancer and cancer therapies. Symptoms of urinary incontinence negatively may affect patients' lifestyles, self-esteem, and quality of life. Although urinary incontinence is not a new problem, nurses often underestimate its impact on patients. Knowledge of the physiology of micturition and causes of urinary incontinence in patients with cancer may help nurses identify patients at risk and provide a framework for conducting targeted assessments of urinary function.

Adult↗
PubMed1998

Endoscopic ultrasound-guided real-time fine-needle aspiration: clinicopathologic features of 60 patients.

Diagnosis of lesions of the gastrointestinal tract and adjacent structures is possible using an imaging modality, endoscopic ultrasonography (EUS). Fine-needle aspiration (FNA) is a suitable and cost-effective technique for obtaining cytohistologic material to confirm the diagnosis. EUS is capable of both characterizing the lesion and then guiding the FNA under real-time (RT) ultrasound guidance using a through-the-scope needle aspiration system. The goal of this study was to determine the diagnostic accuracy of this technique and to describe the clinicopathologic features. Sixty patients underwent EUS-guided RTFNA of 64 lesions, including pancreas (n = 45), periluminal lymph nodes (n = 12), mediastinal and retroperitoneal masses (n = 4), and hepatobiliary masses (n = 3). Follow-up data were obtained by surgery, histopathology, or clinical course. Thirty-one lesions were malignant, eight were atypical/suspicious, 16 were non-neoplastic, and nine were non-diagnostic. Of the 55 lesions with sufficient material for interpretation, 54 had follow-up confirmation of the RTFNA diagnosis. The calculated sensitivity and specificity for malignancy was 90% and 100%, respectively. Diagnostic accuracy for malignancy was excellent for gastrointestinal associated lymph nodes (100%), mediastinal and retroperitoneal masses (100%), somewhat less so for pancreatic tumors (94%), and poor for hepatobiliary lesions (33%). EUS-guided RTFNA is accurate for sampling small gastrointestinal tract-associated lesions. EUS-guided RTFNA should be considered as a procedure of choice in selected patients when the results will influence management decisions.

Abdominal Neoplasms↗
PubMed1998

Mechanomyographic and electromyographic responses to eccentric and concentric isokinetic muscle actions of the biceps brachii.

The purpose of the present investigation was to examine the effects of forearm angular velocity on the mechanomyographic (MMG) and electromyographic (EMG) responses to eccentric and concentric isokinetic muscle actions. Ten adult male volunteers (mean+/-SD age=23+/-2 years) performed maximal eccentric and concentric muscle actions of the forearm flexors at 30 degrees, 90 degrees, and 150 degrees s(-1). There was no significant (P> 0.05) velocity-related change in peak torque (PT) for the eccentric muscle actions, but there was a significant (P < 0.05) decrease in PT for the concentric muscle actions. For the eccentric and concentric muscle actions, there was a significant (P< 0.05) velocity-related increase in MMG amplitude. There was no significant (P < 0.05) change in EMG amplitude across velocity for the eccentric or concentric muscle actions. The results indicated velocity-related dissociations among the PT, MMG, and EMG responses to maximal eccentric and concentric isokinetic muscle actions.

Adult↗
PubMed1998

The aortic valve microstructure: effects of transvalvular pressure.

We undertook this study to establish a more quantitative understanding of the microstructural response of the aortic valve cusp to pressure loading. Fresh porcine aortic valves were fixed at transvalvular pressures ranging from 0 mmHg to 90 mmHg, and small-angle light scattering (SALS) was used to quantify the gross fiber structure of the valve cusps. At all pressures the fiber-preferred directions coursed along the circumferential direction. Increasing transvalvular pressure induced the greatest changes in fiber alignment between 0 and 1 mmHg, with no detectable change past 4 mmHg. When the fibrosa and ventricularis layers of the cusps were re-scanned separately, the fibrosa layer revealed a higher degree of orientation while the ventricularis was more randomly oriented. The degree of fiber orientation for both layers became more similar once the transvalvular pressure exceeded 4 mmHg, and the layers were almost indistinguishable by 60 mmHg. It is possible that, in addition to retracting the aortic cusp during systole, the ventricularis mechanically may contribute to the diastolic cuspal stiffness at high transvalvular pressures, which may help to prevent over distention of the cusp. Our results suggest a complex, highly heterogeneous structural response to transvalvular pressure on a fiber level that will have to be duplicated in future bioprosthetic heart valve designs.

Animals↗