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Biomedical subjects

A J Bailey

Publications and source records attributed to A J Bailey.

At least 91 records · Page 5Linked to original sources

Interdisciplinary integration for quality improvement: the Cleveland Veterans Affairs Medical Center Firm System.

BACKGROUND: Many of the characteristics of Firm Systems lend themselves to the application of principles of continuous quality improvement (CQI). A Firm System is defined as two or more parallel practices organized on the principle of continuity of relationships between patients and an interdisciplinary group of health care professionals and trainees. Firm Systems are organized around the care of the patient or customer and emphasize access, continuity, and quality of care. CASE STUDY: The Firm System was implemented at the Cleveland Veterans Affairs Medical Center (VAMC) not as a CQI initiative per se, but as an effort to coordinate the processes involved in the delivery of patient care. The primary goals of this implementation were to improve the quality of patient care, medical education, and health care research. The main strategy to deal with problems caused by uncoordinated care were to move from a departmental approach to an integrated interdisciplinary approach. This approach represented a paradigm shift within the organization that extended to planning, documentation, and the general work environment. Most important, the institution had leaders who were committed to the Firm System and willing to authorize resources to ensure its success. CONCLUSION: VA hospitals are ideal settings for Firm Systems because they provide longitudinal, comprehensive care with a centralized, prepaid payment mechanism, and they have well-developed information systems that allow the random assignment of patients to Firms. Recommendations to others interested in implementing Firm Systems include creation of a written plan that can gain general support; identification of resources needed for successful implementation; remembering that the patient is the most important customer, as well as that complex systems have many customers; monitoring of performance; and the importance of randomizing patients and providers.

Continuity of Patient Care↗

Abnormal collagen cross-linking in the cartilage of a diastrophic dysplasia patient.

The abnormal organization of the cartilage collagen in diastrophic dysplasia is not generally reflected in the levels of the major stabilizing cross-link, hydroxylysyl-pyridinoline. However, in one case there was a marked decrease in the pyridinoline concomitant with the appearance of two unknown components in the cross-link region of the chromatogram. A decrease in cross-linking of this magnitude could lead to mechanically weakened cartilage. Insufficient material was available to characterize these unknown components. The disorganization of cartilage in some cases of diastrophic dysplasia could therefore be due to post-translational modifications, including defective cross-linking.

Amino Acids↗

Preparation of Bruch's membrane and analysis of the age-related changes in the structural collagens.

AIMS/BACKGROUND: The morphological changes in Bruch's membrane and its constituent collagen seen during aging have been studied extensively but the chemical nature of the collagen and any aging changes have not previously been evaluated. METHODS: A method for preparing purified Bruch's membrane from human cadaver eyes by dissection preceded by trypsin digestion was developed. Following pepsin digestion, the constituent collagens were analysed by SDS-PAGE and by immunoblotting. Cyanogen bromide digestion was used to ascertain the solubility of the collagen and the proportion of type I to type III collagen. After hydrolysis of Bruch's membrane samples the constituent amino acids and collagen crosslinks were measured. RESULTS: The presence of collagen types I, III, IV, and V in Bruch's membrane was confirmed. The proportion of type III collagen as a percentage of total fibrous collagens was calculated as being between 35% and 39%, with no significant difference between different macular and peripheral sites or with age. There was a highly significant decline in the solubility of Bruch's membrane collagen with age, from near 100% in the first decade of life to 40-50% in the ninth decade at both macular and peripheral sites. There was no significant change in the amount of enzymatically formed collagen crosslinks with age. Amino acid analysis indicated a significant increase in the amount of non-collagen protein with age in macular but not peripheral sites. CONCLUSION: Changes in the constituent collagens may contribute to the accumulation of debris in Bruch's membrane with age and interfere with the function of the retinal pigment epithelium, with subsequent consequences for the overlying photoreceptors.

Adolescent↗

The continuous elongation technique for severe Dupuytren's disease. A biochemical mechanism.

Continuous extension of Dupuytren's contracture prior to fasciectomy results in a softening of the tissue, allowing straightening of the fingers. The observed change in cross-link profile indicates an increase in newly synthesised collagen due to increased turnover. This was confirmed by demonstration of the increases in levels of the degradative enzymes, the neutral metalloproteinases, collagenase and gelatinase and the acidic cathepsins B and L. Both types of enzyme effectively depolymerize the collagen fibres, albeit by different mechanisms, leading initially to loss of tensile strength and ultimately to solubilization. We suggest that the increase in enzyme activity is generated by tension on the fibroblasts of this metabolically active tissue produced during the continuous extension of the retracted fingers. The weakening of the fibres by degradation and the increase in newly synthesized collagen provide an explanation for the extension of the tissue without trauma.

Amino Acids↗

Poisoned landscapes: the epidemiology of environmental lead exposure in Massachusetts children 1990-1991.

This research models the geographic variation in lead poisoning among children living in Massachusetts between 1990 and 1991. Elevated levels of blood lead, which reduce educational performance, arise because children are exposed to unnaturally concentrated sources of lead in the built environment. A Poisson regression model indicates that a large number of children with lead poisoning may be detected in towns with a high proportion of older housing, female headed households, African-Americans, and an industrial heritage. Our results suggest links between the processes of urbanization and industrialization in Massachusetts and today's lead poisoned landscapes.

Child, Preschool↗

Migration and unemployment duration among young adults.

"The relationship between migration and unemployment duration is examined. Standard job search predictors of spell length (replacement income, labor force experience, personal characteristics and economic conditions) are included as control variables alongside measures of migration in a Weibull hazard model. The model is estimated using data from the [U.S.] National Longitudinal Survey of Youth. Young adults who migrated while unemployed had longer durations of unemployment than those who did not migrate. The rate at which they found jobs was also linked to how long they had been unemployed, to being laid off, being African American, to going to college, having a mortgage and to national unemployment conditions."

Americas↗

Differential scanning calorimetric studies of superficial digital flexor tendon degeneration in the horse.

Differential scanning calorimetry (DSC) of equine superficial digital flexor tendons revealed the presence of a small exothermic peak at 23 degrees C of unknown origin, and a large endothermic peak at 70 degrees C due to denaturation of cross-linked collagen fibres. In the central degenerated core of damaged tendons the denaturation temperature remained at 70 degrees C but the enthalpy decreased in relation to the extent of degeneration of the tendon. We suggest that this reduction in enthalpy is due to depolymerisation and denaturation of the collagen fibres. This contention is supported by the observed increased activity of the degradative enzyme cathepsin B secreted by the fibroblasts. DSC analysis of cultured porcine tendon fibroblasts revealed a multicomponent endotherm, denaturation beginning at 46 degrees C, a temperature capable of being achieved within the tendon during intensive exercise. DSC clearly has considerable potential in complementing morphological and biochemical studies to determine the aetiology and progress of equine tendon degeneration.

Animals↗

Changes in collagen composition and cross-links in bone and skin of osteoporotic postmenopausal women treated with percutaneous estradiol implants.

OBJECTIVE: To determine the effects of percutaneous estradiol (E2) implants on the collagen composition and maturity in the bone and skin of osteoporotic postmenopausal women. METHODS: Sixteen postmenopausal women with low bone mineral density were treated for 1 year with 75-mg E2 implants. Iliac crest bone and skin biopsies were analyzed for collagen content and collagen cross-links before treatment and at 1 year. Dual energy x-ray absorptiometry of the lumbar spine and proximal femur was also performed before and after 1 year of therapy. RESULTS: The cortical bone showed a significant increase in the mature cross-links of both hydroxylysylpyridinoline (P < .01) and lysylpyridinoline (P < .01), with a significant reduction in the percentage of collagen (P < .001). The pattern was similar in trabecular bone, with lysylpyridinoline increasing significantly (P < .05). The skin exhibited a significant reduction in the immature cross-link hydroxylysinonorleucine (P < .01), but no significant change in the percentage of collagen content or the mature cross-link histidinohydroxylysinonorleucine. The median increases in bone density were 11.5% at the spine and 4.34% at the total hip. The median post-treatment serum E2 level was 639 pmol/L. CONCLUSIONS: Bone mineral density increased at all the sites measured in the spine and proximal hip. The quality of the collagen within the transiliac biopsies had matured in that the concentration of the mature collagen cross-links had increased. These findings support a reduction in the turnover of bone collagen following estrogen replacement therapy. More important, the formation of a more mature collagen fiber should help to reduce the risk of future bone fracture.

Absorptiometry, Photon↗

Chemistry of collagen cross-links: glucose-mediated covalent cross-linking of type-IV collagen in lens capsules.

The incubation of lens capsules with glucose in vitro resulted in changes in the mechanical and thermal properties of type-IV collagen consistent with increased cross-linking. Differential scanning calorimetry (d.s.c.) of fresh lens capsules showed two major peaks at melting temperatures Tm 1 and Tm 2 at approx. 54 degrees C and 90 degrees C, which can be attributed to the denaturation of the triple helix and 7S domains respectively. Glycosylation of lens capsules in vitro for 24 weeks caused an increase in Tm 1 from 54 degrees C to 61 degrees C, while non-glycosylated, control incubated capsules increased to a Tm 1 of 57 degrees C. The higher temperature required to denature the type-IV collagen after incubation in vitro suggested increased intermolecular cross-linking. Glycosylated lens capsules were more brittle than fresh samples, breaking at a maximum strain of 36.8 +/- 1.8% compared with 75.6 +/- 6.3% for the fresh samples. The stress at maximum strain (or 'strength') was dramatically reduced from 12.0 to 4.7 N.mm.mg-1 after glycosylation in vitro. The increased constraints within the system leading to loss of strength and increased brittleness suggested not only the presence of more cross-links but a difference in the location of these cross-links compared with the natural lysyl-aldehyde-derived cross-links. The chemical nature of the fluorescent glucose-derived cross-link following glycosylation was determined as pentosidine, at a concentration of 1 pentosidine molecule per 600 collagen molecules after 24 weeks incubation. Pentosidine was also determined in the lens capsules obtained from uncontrolled diabetics at a level of about 1 per 100 collagen molecules. The concentration of these pentosidine cross-links is far too small to account for the observed changes in the thermal and mechanical properties following incubation in vitro, clearly indicating that another as yet undefined, but apparently more important cross-linking mechanism mediated by glucose is taking place.

Animals↗

Characterisation of TNF-alpha-related peptides by high-performance liquid chromatography-mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry.

Ion-spray triple quadrupole mass spectrometry and high-performance liquid chromatography were used to investigate the products from the solid phase synthesis of (H)-Leu-Thr-Glu-Asn-(OH), a TNF-alpha active-site probe. The target sequence was assembled using tert.-butoxycarbonyl (Boc) chemistry in stepwise fashion from the C-terminal on an Boc-Asn-OCH2-Pam-copoly(styrene-divinylbenzene) resin [Pam = 4-(carboxamidomethyl)benzyl ester]. The crude product was deprotected and cleaved from the resin by HF-p-cresol treatment for 1 h at 0 degrees C. HPLC analysis at 214 nm indicated two late-eluting major products and an early-eluting product. Preparative HPLC demonstrated that the early-eluting product contained ca. 80% of the expected recovered sample mass. Each component was then directly analysed by mass spectrometry and tandem mass spectrometry. The early eluting peak was confirmed as the desired LTEN sequence. Synthesis of the same sequence using 9-fluorenyl methoxycarbonyl (Fmoc) chemistry gave an identical product and confirmed the above analysis. The most significant by-product was derived from arylation of the glutamyl group by the quencher p-cresol. The likely origins of the by-products are discussed.

Amino Acid Sequence↗

Reductive cleavage of the disulfide bonds of the collagen IV noncollagenous domain in aqueous sodium dodecyl sulfate: absence of intermolecular nondisulfide cross-links.

The subunits of the collagen IV hexameric, noncollagenous NC1 domain obtained from bovine aorta, glomerular basement membrane, alveolar basement membrane and placental basement membrane are predominantly dimers. A large fraction of the dimers had been thought to be linked by nondisulfide bonds because they were resistant to cleavage by 5% (v/v) 2-mercaptoethanol, 2% (w/v) SDS, at 100 degrees C. However, if an unusually high concentration of 2-mercaptoethanol, e.g., 40% (v/v), is used, complete conversion of dimers into monomers is achieved, indicating the lack of intersubunit nondisulfide cross-links. Electrophoresis patterns indicate that some of the intermolecular disulfide bonds of the dimers are more resistant to reduction in aqueous SDS than are some of the intramolecular disulfide bonds.

Alkylation↗

Migration history, migration behavior and selectivity.

"A series of proportional hazards models are used to study the relationship between migration history and migration behavior for a sample of young adults from the [U.S.] National Longitudinal Survey of Youth. The results support the argument that migration is a selective process. College educated young adults have a greater hazard rate of making an initial migration but a lower hazard rate of re-migration, suggesting they have less need of corrective geographic behavior. Individuals who have moved two or more times are less responsive to national unemployment conditions than first time migrants. Migration is related to the timing of unemployment within a sojourn. The findings suggest that migrant stock is an important determinant of how labor markets function."

Americas↗

Hamilton Health Sciences Laboratory Program: a provider developed model for hospital, university and community laboratory services.

Clinical Laboratory Sciences are under pressure to reduce the number of tests and cut staff and supply costs. The ability of academic centres to continue to deliver high quality service, teaching and research is threatened. In difficult economic times imaginative strategies are needed to look for solutions which will permit continued advancement in academic and clinical standards. Rationalization of service and cost-effective use of resources are not new concepts; however, there is a scarcity of models which have been developed and promoted by the providers of laboratory services, rather than those imposed by governments and other paying agencies. A model developed and evolved over the last two decades by The Hamilton Health Sciences Laboratory Program (HHSLP) is outlined.

Data Collection↗

Biochemical changes in the collagen of human osteoporotic bone matrix.

Although it is known that collagen imparts mechanical strength to bone no detailed biochemical analysis has been made of osteoporotic bone collagen. We report for the first time significant changes in the properties of the collagen. Analysis of collagen types revealed little change in the proportion of Type III collagen, but in some cases there was a significant loss of the Type VI. However, the major differences were observed in the post-translational modifications, namely, in the stabilizing cross-links and the hydroxylation of the collagen. These changes indicated a higher turnover in the head region compared to the neck region of the femoral head and are consistent with the susceptibility of the neck region to fracture. Clearly, the collagen is altered in osteoporosis and these changes may play a role in the pathogenesis of the disease.

Aged↗

Quantitative analysis of collagen and elastin cross-links using a single-column system.

The separation of both the immature and mature cross-links present in collagen together with the stable cross-links of elastin has been achieved on a single ion-exchange column. This technique avoids the current necessity for two different systems, ion-exchange and high-performance liquid chromatography-fluorescence techniques. The value of the method is illustrated by the comparison of the cross-link contents of aging bovine skin, from foetal to old age.

Aging↗

Post-translational modifications in the collagen of human osteoporotic femoral head.

No detailed biochemical analysis has been made of the possible compositional changes in the collagen relating to the fragility of osteoporotic bone. We report for the first time significant changes in the compositional properties of the collagen. The major differences were observed in the post-translational modifications, namely, in the hydroxylation of lysine residues and the nature of the stabilizing cross-links of the collagen fibre. The increase in hydroxylation was greater in the head region compared to the neck region of the femoral head, whilst the decrease in the intermediate cross-links was greater in the neck region. Clearly, the collagen is altered in osteoporosis and it is important that these changes are recognised in studies of bone metabolism in osteoporosis since they may play a role in the pathogenesis of the disease.

Adult↗

Effect of chemical modifications on the susceptibility of collagen to proteolysis. II. Dehydrothermal crosslinking.

Collagen was dehydrothermally treated (heat cured) by heating dry under vacuum at 60, 80, 100 and 120 degrees C. The change in stability was determined by subjecting to measurement of gross crosslinking, content of lysino-alanine and naturally occurring collagen crosslinks, shrinkage temperature (TM), susceptibility to digestion by lysosomal thiol proteases, and susceptibility to pepsin and trypsin. Morphological changes were examined by electron microscopy. The in vivo biodegradation of dehydrothermally treated collagen sponges was investigated using a rat lumbar muscle implantation model for up to 28 days. For all heat-cured collagens, the data strongly indicated that both crosslinking and denaturation/degradation was present in increasing quantities with increasing temperature of treatment, its level was too low (maximum 179 pmol mg-1) to account for the decreased solubility and increased molecular weight gross changes observed. Increasing resistance of treated collagen to both lysosomal cathepsins and pepsin correlated well with increased crosslinking and increasing temperature of the heat-curing process. However, increased denaturation/degradation of the collagen at higher temperatures was revealed by electrophoretic analysis, trypsin hydrolysis data and by electron microscopy. Differential scanning calorimetry (d.s.c.) correlated well with these results showing an increased level of denaturation in heated samples. The in vivo study showed little difference between control and heat-cured samples except for the material treated at 120 degrees C which was biodegraded in vivo at a significantly faster rate. The data shows, therefore, that crosslinking induced by the dehydrothermal treatment of collagen decreases its rate of proteolysis at acid pH in vitro. However, the simultaneous denaturation/degradation of the protein during the heat-cure process appears to be a more important factor in determining the fate of the material implanted into rat muscle.

Animals↗