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Biomedical subjects

F Nelson

Publications and source records attributed to F Nelson.

At least 19 recordsLinked to original sources
PubMed2005

Early post-traumatic osteoarthritis-like changes in human articular cartilage following rupture of the anterior cruciate ligament.

OBJECTIVE: Injury to the anterior cruciate ligament (ACL) frequently leads to post-traumatic osteoarthritis (OA). In this study we determined whether early degenerative changes characteristic of idiopathic OA are induced in articular cartilage following ACL injury. METHODS: A small sample of femoral articular cartilage was removed at surgery, as part of ACL reconstruction, from a total of 50 patients with ACL injuries. Of these, 28 underwent surgery less than 1 year post-injury. Control cartilages were obtained from the same site from 21 persons at autopsy. All cartilages were examined for molecular changes. The content of type II collagen, its cleavage by collagenases and its denaturation were determined by immunoassay. The total content of glycosaminoglycan (GAG), which is principally aggrecan, was measured colorimetrically. Data were expressed per unit DNA (GAG and collagen content) or as a percentage of total collagen cleaved or denatured. Other cartilages from the same site (8 controls, 12 less than 1 year and 8 more than 1 year post-injury) were frozen sectioned and examined histologically to determine by Mankin grading cartilage degeneration. RESULTS: Histological analyses revealed that control subjects exhibited staining for proteoglycan, which was reduced in some patients following ACL rupture. Degeneration of the articular surface was sometimes observed 1 year after ACL rupture. Although the Mankin grade increased with time after rupture these changes were not significant. Immunoassays, however, revealed an increase in GAG content within 1 year which was maintained after 1 year although no longer significant. No changes in total type II collagen content were observed during the period of study. However, there were significant increases in the denaturation and cleavage of type II collagen less than and more than 1 year post-ACL rupture. Total type II collagen content was directly correlated with GAG content in all three groups, with the significance being weakest at more than 1 year. After 1 year an inverse correlation was observed between total type II collagen content and collagen cleavage as well as denaturation. CONCLUSIONS: These observations reveal that joint instability resulting from ACL injury rapidly results in degenerative changes characteristic of those seen in idiopathic OA at arthroplasty and in experimental OA following ACL surgery. These changes may contribute to the development of post-traumatic OA that is commonly observed following ACL injury. The observations support and extend conclusions from other studies on human and animal articular cartilage and synovial fluids post-ACL injury that have revealed a rapid onset of damage to type II collagen and an initial increase in proteoglycan content characteristic of experimental OA post-ACL injury. This study provides direct evidence for the rapid development of degenerative changes characteristic of OA following ACL injury.

Adolescent↗
PubMed2000

Selective enhancement of collagenase-mediated cleavage of resident type II collagen in cultured osteoarthritic cartilage and arrest with a synthetic inhibitor that spares collagenase 1 (matrix metalloproteinase 1).

OBJECTIVE: To examine whether type II collagen cleavage by collagenase and loss of proteoglycan are excessive in human osteoarthritic (OA) articular cartilage compared with nonarthritic articular cartilage, and whether this can be inhibited by a selective synthetic inhibitor that spares collagenase 1 (matrix metalloproteinase 1 [MMP-1]). METHODS: Articular cartilage samples were obtained during surgery from 11 patients with OA and at autopsy from 5 adults without arthritis. The articular cartilage samples were cultured in serum-free medium. A collagenase-generated neoepitope, which reflects cleavage of type II collagen, and proteoglycan glycosaminoglycan (GAG), which predominantly reflects aggrecan release, were assayed in culture media. In addition, cultures were performed using either of 2 synthetic MMP inhibitors, both of which inhibited collagenase 2 (MMP-8) and collagenase 3 (MMP-13), but one of which spared collagenase 1. Cultures were also biolabeled with 3H-proline in the presence and absence of these inhibitors to measure collagen synthesis (as tritiated hydroxyproline) and incorporation in articular cartilage. RESULTS: As a group, cleavage of type II collagen by collagenase was significantly increased in OA cartilage samples. In contrast, proteoglycan (GAG) release was not increased. This release of a collagenase-generated epitope was inhibited by both MMP inhibitors in 2 of 5 nonarthritic samples and in 9 of 11 OA cartilage samples. The inhibitor that spared collagenase 1 was generally more effective and inhibited release from 4 of 5 nonarthritic cartilage samples and the same OA cartilage samples. Group analyses revealed that the inhibition of collagenase neoepitope release by both inhibitors was significant in the OA patient cartilage, but not in the nonarthritic cartilage. Proteoglycan loss was unaffected by either inhibitor. Newly synthesized collagen (predominantly, type II) exhibited increased incorporation in OA cartilage, but only in the presence of the inhibitor that arrested collagenase 1 activity. CONCLUSION: These results further indicate that the digestion of type II collagen by collagenase is selectively increased in OA cartilage, and that this can be inhibited in the majority of cases by a synthetic inhibitor that can inhibit collagenases 2 and 3, but not collagenase 1. The results also suggest that in OA, newly synthesized collagen is digested, but in a different manner than that of resident molecules. Proteoglycan release was not increased in OA cartilage and was unaffected by these inhibitors. Inhibitors of this kind may be of value in preventing damage to type II collagen in human arthritic articular cartilage.

Adult↗
PubMed2000

Perceptions of the role of the school in providing information and support to adolescent children of women with breast cancer.

Little is known about the needs of adolescents of women with breast cancer. The purpose of this study was to describe the perceptions of adolescents (ages 12-20) about the role of the school in assisting them in dealing with the cancer experience. An exploratory, qualitative study was done to elicit detailed descriptions of adolescent's needs for information and support in response to their mother's breast cancer. A convenience sample of 31 adolescents of women in five illness phases participated in semi-structured interviews. In addition, two focus group interviews were conducted. Interviews were tape-recorded, transcribed and analysed using content analysis techniques. Findings specific to the adolescents' perceptions of the role of the school were discussed according to content, type, amount, timing, provider and quality of information. Support needs were discussed as type of support, source of support, amount, timing and focus. Although school personnel attempted to be supportive and adolescents received generic information about cancer, overall the needs of the adolescents were not adequately addressed. Recommendations for schools and health services in assisting adolescents to cope with this major life experience are made.

Adolescent↗
PubMed1998

Evidence for altered synthesis of type II collagen in patients with osteoarthritis.

There is evidence to suggest that the synthesis of type II collagen is increased in osteoarthritis (OA). Using an immunoassay, we show that the content of the C-propeptide of type II procollagen (CPII), released extracellularly from the newly synthesized molecule, is directly related to the synthesis of this molecule in healthy and osteoarthritic articular cartilages. In OA cartilage, CPII content is often markedly elevated (mean 7.6-fold), particularly in the mid and deep zones, reaching 29.6% of the content in newborn. Synthesis is also directly related to total collagen II content in OA, suggesting its importance in maintaining collagen content and cartilage structure. The release of CPII from cartilage is correlated directly with cartilage content. However, the increase in CPII in OA cartilage is not reflected in serum, where a significant reduction is observed. Together these studies provide evidence for alterations in procollagen II synthesis in vivo in patients with OA.

Adult↗
PubMed1998

Pineal opioid receptors and analgesic action of melatonin.

Physicians have noted since antiquity that their patients complained of less pain and required fewer analgesics at night times. In most species, including the humans, the circulating levels of melatonin, a substance with analgesic and hypnotic properties, exhibit a pronounced circadian rhythm with serum levels being high at night and very low during day times. Moreover, melatonin exhibits maximal analgesic effects at night, pinealectomy abolishes the analgesic effects of melatonin, and mu opioid receptor antagonists disrupt the day-night rhythm of nociception. It is believed that melatonin, with its sedative and analgesic effects, is capable of providing a pain free sleep so that the body may recuperate and restore itself to function again at its peak capacity. Moreover, in conditions when pain is associated with extensive tissue injury, melatonin's ability to scavenge free radicals and abort oxidative stress is yet another beneficial effect to be realized. Since melatonin may behave as a mixed opioid receptor agonist-antagonist, it is doubtful that a physician simply could potentiate the analgesic efficacy of narcotics such as morphine by coadministering melatonin. Therefore, future research may synthesize highly efficacious melatonin analogues capable of providing maximum analgesia and hopefully being devoid of addiction liability now associated with currently available narcotics.

Analgesia↗
PubMed1997

Evaluation of an interdisciplinary training program in palliative care: addressing the needs of rural and northern communities.

Our study was a pilot test of an interdisciplinary training program in palliative care to improve the quality of care to terminally ill cancer and AIDS patients in rural and northern communities in Manitoba. The program involved two weeks of intense palliative care training for nurses, social workers, physicians, and volunteers. Four teams were trained during a six-month period. A repeated measures design was used to assess the effectiveness of the program. Results indicated that health professionals' knowledge about care of the dying, care of individuals with HIV/AIDS, and attitudes toward care of the dying improved upon completion of the training program and remained improved three months following the program. Improvements in use of medications, increased attention to family care, increased discussion of DNR orders, and increased consultation related to symptom management were evident following the training program. The parallel training program for volunteers was also judged to be effective.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.

Adult↗
PubMed1996

Case management: meeting the needs of chronically ill patients in an HMO.

Primary care staff education plays a critical role in a health plan making a transition from a case management model to a model that emphasizes close care coordination for chronically ill patients with multiple care needs. Multidisciplinary teams can help refine the system to have a positive impact on care across diverse settings: Health Plan of Nevada found that such training aids staff in identifying at-risk individuals and in developing plans for preventive health screening activities, medication compliance, and needs assessment.

Activities of Daily Living↗
PubMed1993

Ultrastructural heterogeneity in undifferentiated bronchial carcinoma.

Electron microscopy is often suggested as a useful aid to the classification of light microscopically undifferentiated bronchial malignancies, features such as dense-core vesicles, desmosomes or tonofilaments, and microacini, allowing their designation as endocrine, squamous, or adenocarcinomas respectively. However, there is no reason to suppose that the heterogeneity of malignant bronchial tumours so often apparent by light microscopy or on immunolabelling might not occur at the ultrastructural level too. Extensive sampling of all deposits from eight subjects coming to necropsy with undifferentiated bronchial carcinoma revealed ultrastructural features of glandular and squamous differentiation to be widespread and often to occur together, although dense-core vesicles were not seen in any of the tumours studied. Heterogeneity was present within individual tumour deposits and particularly between different deposits of those tumours which had disseminated, such that any ultrastructural diagnosis would have been significantly influenced by sampling. Such variation should be borne in mind when ultrastructural features are used to classify bronchial malignancies.

Bronchial Neoplasms↗
PubMed1992

Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study.

We have obtained airway mucosal biopsies by fiberoptic bronchoscopy for light and electron microscopic analysis of three distinct airway levels of the left lung in three subject groups. Group A: 11 subjects with mild atopic asthma (mean age, 29 yr; %FEV1, 89 to 116%; mean PC20 histamine, 2.42 mg/ml), each biopsied twice, one prior to 4 wk of treatment with either inhaled terbutaline (250 micrograms, two puffs four times daily; n = 5) or inhaled budesonide (200 micrograms, one puff twice daily; n = 6) followed by a second biopsy to allow determination of the effects of treatment. Group B: 10 subjects with severe asthma receiving long-term (average, 3.7 yr) corticosteroid treatment were biopsied once only (mean age, 28 yr; %FEV1, 86 to 129%; mean PC20 histamine, 1.85 mg/ml). Group C: 12 normal healthy control subjects (mean age, 35 yr; %FEV1, 92 to 135%; PC20 histamine greater than 16 mg/ml) biopsied once. By light microscopy of plastic-embedded sections, Group A asthmatics had an increased cellular infiltrate when compared with either the healthy control group or the Group B asthmatics (p less than 0.05). Both asthma groups had a thickening of basement membrane reticular collagen compared with the healthy control group (p less than 0.01). Compared with the control group, there was an increase in the percentage of the total cells that were mast cells (p less than 0.01) and eosinophils (p less than 0.05) in Group A and of eosinophils (p less than 0.01) and histiocytes (p less than 0.01) in Group B. The results of cell counts by electron microscopy largely supported these findings, and, in addition, they demonstrated an increased frequency of foci of free eosinophil granules and decreased numbers of neutrophils (p less than 0.01). By light microscopy, budesonide reduced the percentage of mast cells and eosinophils (p less than 0.05). But for the percentage of lymphocytes, which increased (p less than 0.05), terbutaline was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Application of microwave irradiation to immunohistochemistry: preservation of antigens of the extracellular matrix.

Microwave irradiation as a means of fixation was evaluated for the preservation of extracellular matrix antigens such as collagen III, IV, fibronectin and laminin in both lung and liver specimens. Small tissue samples were placed in normal saline or periodate-lysine-paraformaldehyde (PLP) and irradiated for 30 sec to bring them to a temperature of 50 C. The tissue was then processed rapidly in a tissue processor adjusted to a 2 hr cycle and embedded in paraffin. Sections were immunostained. For comparison, routine cryostat sections as well as sections of formalin fixed tissue were used. Microwave irradiation in saline gave excellent morphological detail, comparable to that in formalin fixed tissue. All four antigens evaluated were well preserved without the necessity of prior pepsin digestion. Microwave fixation is promising for preservation of antigenicity and morphological detail, and considerably reduces the time required for processing.

Extracellular Matrix↗
PubMed1983

Deaths related to propoxyphene or codeine or both.

Ninety-nine deaths involving propoxyphene or codeine or both were investigated through interviews with surviving relatives and associates. The criterion for admission to this study was the presence of propoxyphene or codeine in the body fluids or tissues, determined analytically. The codeine-related group included more ethnic minority persons, more histories of primary drug addiction, more users of street drugs, and more accidental deaths. In the propoxyphene-related group there were fewer histories of drug addiction and more persons with mental illness and more suicides. Most victims had considerable past experience with one or both of the drugs and other drugs as well. Propoxyphene was usually obtained by physician prescription. Codeine was often obtained illegally.

Adult↗