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Biomedical subjects

D Salter

Publications and source records attributed to D Salter.

At least 19 recordsLinked to original sources
PubMed2006

A tissue engineering approach to meniscus regeneration in a sheep model.

OBJECTIVE: Regeneration of the meniscal tissue occurs to a limited extent, and the loss of meniscal tissue leads to osteoarthritis. A new biomaterial consisting of hyaluronic acid and polycaprolactone was used as a meniscus substitute in sheep to evaluate the properties of the implant material with regard to size, biomechanical stability, tissue ingrowth, and integration. METHODS: Eight sheep (right stifle joints) were treated with three total and three partial meniscus replacements while two meniscectomies served as empty controls. The animals were euthanized after 6 weeks. The specimens were assessed by gross inspection and histology, and compared with the nonoperated left joints. RESULTS: The surgical technique was found to be feasible. The implants remained in position, did not tear, and showed excellent tissue ingrowth to the capsule. Tissue integration was also observed between the original meniscus and the implant. However, graft compression and extrusion occurred. The histological investigation revealed tissue formation, cellular infiltration and vascularization. Cartilage degeneration was more severe in the operated joints. CONCLUSION: The present study shows promising results concerning the qualities of this biomaterial with regard to implantation technique, stability and tissue ingrowth.

Adjuvants, Immunologic↗
PubMed2006

The early response to major trauma and intramedullary nailing.

The stress response to trauma is the summation of the physiological response to the injury (the 'first hit') and by the response to any on-going physiological disturbance or subsequent trauma surgery (the 'second hit'). Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses.

Animals↗
PubMed2005

Osteoarthritis cartilage histopathology: grading and staging.

OBJECTIVE: Current osteoarthritis (OA) histopathology assessment methods have difficulties in their utility for early disease, as well as their reproducibility and validity. Our objective was to devise a more useful method to assess OA histopathology that would have wide application for clinical and experimental OA assessment and would become recognized as the standard method. DESIGN: An OARSI Working Group deliberated on principles, standards and features for an OA cartilage pathology assessment system. Using current knowledge of the pathophysiology of OA morphologic features, a proposed system was presented at OARSI 2000. Subsequently, this was widely circulated for comments amongst experts in OA pathology. RESULTS: An OA cartilage pathology assessment system based on six grades, which reflect depth of the lesion and four stages reflecting extent of OA over the joint surface was developed. CONCLUSIONS: The OARSI cartilage OA histopathology grading system appears consistent and simple to apply. Further studies are required to confirm the system's utility.

Animals↗
PubMed2000

Expression of parathyroid hormone-related protein and its receptor in bone metastases from prostate cancer.

Studies of breast cancer suggest that parathyroid hormone-related protein (PTHrP) is important in the development of bone metastases. To determine whether PTHrP expression is important in prostate cancer metastasis, immunohistochemistry and in situ hybridization were used to assess the expression of PTHrP and its receptor in primary prostate cancer and bone metastases from both prostate and non-prostate cancers. PTHrP was expressed in more prostate primary tumours than bone metastases (p=0.003, Fisher's exact test). All bone metastases from non-prostate cancers expressed PTHrP. In contrast, PTHrP receptor was expressed in all bone metastases, but in only 19% of primary prostate tumours (p=0.001). The receptor to PTHrP was found to be highly expressed in bone metastases from prostate and other primaries, whereas PTHrP protein was found to have lower expression in the bone metastases than in the primary tumours. In conclusion, the expression of the receptor to PTHrP is increased in bone metastases from prostate cancer and may play an important role in their formation.

Bone Neoplasms↗
PubMed1999

Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo.

Resistance to chemotherapy is a principal problem in the treatment of small cell lung cancer (SCLC). We show here that SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) at both primary and metastatic sites. Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resistance to chemotherapeutic agents as a result of beta1 integrin-stimulated tyrosine kinase activation suppressing chemotherapy-induced apoptosis. SCLC may create a specialized microenvironment, and the survival of cells bound to ECM could explain the partial responses and local recurrence of SCLC often seen clinically after chemotherapy. Strategies based on blocking beta1 integrin-mediated survival signals may represent a new therapeutic approach to improve the response to chemotherapy in SCLC.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Evaluation of Japanese quail as a model system for avian transgenesis using avian leukosis viruses.

Vertical transmission of avian leukosis viruses (ALV) can occur genetically through the germline for both male and female chickens but only nongenetically or congenitally through the female. We had previously shown that tolerantly ALV-infected males, from ALV injection into fertile chicken eggs at day of set, can transmit proviral DNA to their progeny through the germline. An attempt was made to repeat this successful retroviral germline insertion technique of chickens in Japanese quail. After an initial difficulty of infecting quail chicks in ovo at day of set with high titer nonpathogenic recombinant and pathogenic ALV, adequate numbers of tolerantly ALV-infected quail were produced by injecting ALV-infected chicken embryo fibroblasts (CEF) at day of set. Tolerantly ALV-infected male and female quail were then mated to nonviremic quail and vertical transmission of ALV to progeny chicks was determined by analyzing blood for viral antigens and proviral DNA using standard techniques. Vertical transmission of ALV was only detected in the progeny of viremic females. Thus, little or no germline transmission of ALV to progeny occurred from viremic males. Tolerantly ALV-infected males and females from congenital ALV infection, which should infect the embryo and presumably the primordial germ cells (PGC) earlier than egg injection, were mated to nonviremic quails. Vertical transmission of ALV to progeny chicks was analyzed as before. Again, vertical transmission of ALV was only detected in the progeny of viremic females. We conclude that Japanese quail will not be useful in avian transgenic studies involving ALV retroviral vectors.

Animals↗
PubMed1997

Avian leukemias and lymphomas: interplay between retroviruses and herpesviruses.

Avian leukemias and lymphomas are caused primarily by retroviruses and herpesviruses. The protooncogenes activated by avian retroviral insertions in B & T-cell lymphomas will be summarized, with discussion on a new common insertion site, bravo, associated with RAV-O LTR insertion. Two novel interactions between avian retroviruses and Marek's disease herpesvirus (MDV) will be described: one involves direct interactions between putative viral oncoproteins and the other integrative recombination between these two viruses.

Alpharetrovirus↗
PubMed1996

Dobutamine stress echocardiography predicts cardiac events in heart transplant patients.

BACKGROUND: Cardiac transplantation is an accepted treatment modality for end-stage heart failure. Coronary artery disease remains a major cause of mortality in the long term after heart transplantation. Despite the high prevalence of coronary artery disease in heart transplant recipients, currently used noninvasive tests as well as invasive tests are highly unreliable in predicting prognosis. We sought to test the hypothesis that the abnormalities induced by dobutamine stress echocardiography (DSE) may be of prognostic value in predicting acute cardiac events and mortality in heart transplant patients. METHODS AND RESULTS: We prospectively studied 86 survivors of orthotopic heart transplantation and followed them for a mean period of 2 years after the DSE. The patients' median age was 51 +/- 10 years, and mean duration since transplant was 57.7 +/- 29 months (range, 3 to 120 months, mean +/- SD). DSE was performed by a standard protocol (dobutamine 5, 10, 20, 30, and 40 micrograms.kg-1.min-1 at 5-minute stages). DSE was defined as positive for development of new or worsening regional wall motion abnormality or failure of augmentation. Nine patients were excluded from analysis (5 because of acute allograft rejection and 4 because of poor acoustic window). Thus, data from 77 patients were analyzed. Fifty-seven of 77 (74%) had positive DSE. After 24 months of follow-up, 19 of 57 patients with abnormal DSE (33%) experienced 22 major cardiac events. In contrast, no event occurred in patients with normal DSE. Of the 19 with cardiac events, there were 7 episodes of heart failure (including 3 deaths), 4 had unstable angina, and 5 died of cardiac causes. Three patients had myocardial infarction, and 3 others died of noncardiac causes. Among the variables examined, the baseline left ventricular ejection fraction was lower (44 +/- 3.8 versus 51 +/- 1.4) and peak wall motion score index was higher (2.01 +/- 0.4 versus 1.44 +/- 0.4) in the patients group with cardiac events than in those without events. CONCLUSIONS: These results suggest that DSE has significant value in predicting prognosis in post-heart transplant patients. Further studies are needed to define the role of DSE as a routine test for predicting prognosis in cardiac transplant recipients.

Adult↗
PubMed1992

The expression of mouse tyrosinase in chick cells in vitro and in vivo when controlled by a constitutive promoter.

Virally introduced mouse tyrosinase expression was checked both in vitro and in vivo in chicken cells and tissues. The results indicate that a constitutive promoter is able to express mouse tyrosinase in a variety of cells and tissues both in vitro and in vivo. Tyrosinase expression is marked by pigment production in situ, which is visible at macroscopic as well as microscopic levels without the use of substrates. It is concluded that tyrosinase can be a valuable marker for tracking gene insertion since it is spontaneously expressed. The expression of tyrosinase in some cells and tissues has a detrimental effect, however, and should be controlled by tissue-specific promoters.

Animals↗
PubMed1990

Suicidal intent, hopelessness and depression in a parasuicide population: the influence of social desirability and elapsed time.

This paper reports the first British study to assess the construct validity of Beck's Hopelessness Scale (HS) and the Beck Depression Inventory (BDI). On the basis of interviews with 50 economically active parasuicide patients, it was confirmed that hopelessness accounts for the relationship between depression and suicidal intent. Moreover, it was shown that social desirability neither confounds the relationship between hopelessness and suicidal intent, nor has any predictive power in explaining variation in suicidal intent. On the other hand, the interval ('elapsed time') between the commencement of the parasuicidal act and of the research interview was significantly and positively correlated with suicidal intent, and elapsed time was a significant predictor of the total score on Beck's Suicidal Intent Scale. Two explanations for this finding are proposed: the first is based on the possibility that elapsed time is an indirect or proxy measure of medical seriousness; the second derives from the likely impact of prolonged hospital stay on the patient's interpretation or understanding of his/her behaviour. Researchers are advised to take into account the moderating effect of elapsed time when designing studies which examine psychological processes in parasuicide.

Adolescent↗
PubMed1990

Five-year reliability of self-reported alcohol consumption.

Reliability of alcohol consumption reported on a self-administered questionnaire was examined in 73 gynecologic outpatients. The questionnaire included quantity-frequency questions on current beverage-specific alcohol use (wine, beer and liquor). The questions were replicated 5 years later for both the earlier period and for current drinking patterns. Results indicated that, in general, original and retrospective data were highly correlated. Only recall of wine, the least frequently drunk beverage, was more highly correlated with current than with original consumption. Frequency of drinking was typically recalled better than quantity per occasion. Beverage-specific absolute alcohol per day (AA) was less reliable than total AA. Retrospective AA values accounted for 86% of the variability in original scores. The heaviest drinkers, however, tended to report disproportionately greater alcohol intake in retrospect. Thus, almost twice as many heavy drinkers were identified on the basis of their retrospective reports compared to those identified by their original reports. Results from this study suggest that considerable confidence can be placed in retrospective reports of total alcohol consumption by nonalcoholic women over a relatively long-term interval and that heavy drinking may be reported more accurately retrospectively than currently.

Adult↗
PubMed1986

Flexible medullary nailing of tibial shaft fractures.

Fifty-two tibial shaft fractures in 50 patients were treated with flexible medullary nails (Ender type). In 32 cases the fracture was closed and in the remaining 28 cases the fracture was open. Forty-eight of the 52 fractures united in an average time of 16.8 weeks and there were no cases of deep infection or osteomyelitis. Nonunion in four patients required a secondary procedure to obtain union. Flexible medullary nailing is an excellent method for fixation of tibial shaft fractures because it combines the benefits of closed nailing and functional bracing while minimizing the disadvantages of each. Three-point fixation within the medullary canal maintains length alignment and avoids rotational problems. Nailing is done by closed methods without reaming. The technique allows early weight-bearing in a patellar tendon bearing cast or functional brace. Dynamic controlled motion at the fracture site leads to early callus formation which is biomechanically and biologically favorable. The procedure is relatively easy to perform, short in duration, and requires little specialized equipment. Flexible medullary nailing is an alternative treatment modality for selected open and closed displaced tibial shaft fractures.

Adolescent↗
PubMed1985

Comparison of neutralization and DNA restriction enzyme methods for typing clinical isolates of human adenovirus.

Sixty-five adenovirus isolates collected over a 3.5-year period were typed by both standard microneutralization techniques and restriction endonuclease digestion of viral DNA. Of the 65 isolates, 47 (72.3%) representing six adenovirus types could be typed by microneutralization. Eighteen isolates demonstrated partial neutralization with standard antisera to two or more adenovirus serotypes and thus could not be definitively typed. DNA analysis permitted typing of 64 of the 65 isolates (98.5%) (including four isolates which contained mixtures of two adenovirus types), and 12 different types were identified. Neutralization and DNA typing disagreed for five isolates, and in each case, digestion with multiple restriction endonucleases and DNA hybridization studies were consistent with the type assigned by DNA analysis. In addition, the DNA analysis method allowed the identification of genomic variants (genome types) of five adenovirus types. We conclude that typing clinical isolates of adenovirus by restriction endonuclease digestion of viral DNA can be done rapidly, provides additional epidemiological and typing information, and provides fewer ambiguous results than does typing by neutralization.

Adenoviruses, Human↗
PubMed1985

Humoral immune response to herpes simplex virus type 2 glycoproteins in patients receiving a glycoprotein subunit vaccine.

Serial serum specimens from 22 herpes simplex virus (HSV)-seronegative recipients of an HSV type 2 (HSV-2) glycoprotein subunit vaccine were analyzed by radioimmunoprecipitation and polyacrylamide gel electrophoresis for the development of antibodies to HSV-2 gB, gD, and g80, a complex of gC and gE. Volunteers received 50 (n = 12) or 100 micrograms (n = 10) of vaccine at days 0, 28, and 140; sera were drawn weekly for 8 weeks and again at days 140, 147, and 365. Among seronegative volunteers, antibody to gB was detected 2 weeks after the first dose, while antibodies to g80 and gD were detected after the second dose (day 35). Antibodies to nonglycosylated HSV-specific proteins were not detected. A dose-response effect between recipients of 50- and 100-micrograms doses was observed in the proportion of vaccine recipients seroconverting to g80 and in the proportion of recipients retaining antibodies to both gD and g80 over time. Diminishing complement-independent neutralizing antibody titers occurred after the second dose and were associated with loss or reduction of detectable antibody to gD. Volunteers who were seropositive for HSV-1-specific antibody (n = 11) were also enrolled in the trial and received 50-micrograms doses of vaccine. Vaccination resulted in conversion to HSV-2 complement-independent neutralizing antibody specificity or indeterminant specificity in 10 of 11 volunteers. These shifts were accompanied by changes in the radioimmunoprecipitation and polyacrylamide gel electrophoresis profile. These changes, which were apparent by 14 days after the first vaccine dose, included de novo appearance or increased levels of antibody to g80 and increased levels of antibody to gD and gB. These studies document the immunogenicity of solubilized glycoproteins gB, gD, gC, and, possibly, gE in humans.

Antibodies, Viral↗