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Biomedical subjects

D M Smith

Publications and source records attributed to D M Smith.

496 records · Page 28Linked to original sources
PubMedDate not supplied

Effect of prostaglandin on the composition of chinchilla middle ear effusion.

Prostaglandins (PGs) are naturally occurring, cyclic, unsaturated fatty acids which possess a wide range of potent biological activities. PGs have been found in human middle ear effusions and might have implications for understanding the inflammation and possibly the bone resorption seen in chronic otitis media. We have measured PGs by radioimmunoassay in middle ear effusions (MEE) from experimentally induced serous otitis media (SOM) and purulent otitis media (POM) in chinchillas. PGE2 levels were significantly higher in the POM group compared to the SOM group. We have also demonstrated that chinchilla middle ear mucosa can convert arachidonic acid (AA), a precursor of PGs, to PG by injecting 14C-AA into bullae and assaying using radiochromatography. This conversion was completely blocked by both indomethacin and aspirin given orally or by direct injection into the middle ear. We then injected 50 microgram of PGE2 into chinchilla bullae to assess its effect on the composition of MEE. First, the time course of PGE2 metabolism after its injection into the middle ear (ME) was determined by thin-layer chromatography (TLC) of labelled and unlabelled PGE2. Following this, serial daily injections of PGE2 and normal saline as control were made for one, three, and seven days. MEE and serum were collected and assayed for lactate dehydrogenase (LDH), acid and alkaline phosphatase, calcium, protein and hexosamine. Compared to the control, the levels of LDH, acid and alkaline phosphatase, calcium and protein were significantly elevated. Hexosamine levels were higher than the control at one and three days but did not differ significantly at seven days from the control. We have therefore demonstrated that chinchilla middle ear mucosa has the ability to synthesize PG from AA and suggest an active role for PGs in the inflammation and in the bone resorption seen in otitis media.

Animals↗
PubMedDate not supplied

Prostaglandins and otitis media: studies in the chinchilla.

Prostaglandins (PG) are naturally occurring, cyclic, unsaturated fatty acids that possess a wide range of potent biologic activities. Prostaglandins have been found in human middle ear effusions and may have implications for understanding the inflammation and, possibly, the bone resorption seen in chronic otitis media. In the study presented, PGs were measured by radioimmuno-assay in middle ear effusions from experimentally induced serous and purulent otitis media in chinchillas. The ability of chinchilla middle ear mucosa to synthesize PGs from 14C-arachidonic acid was also demonstrated. The authors suggest an active role for PGs in the inflammation and the bone resorption seen in otitis media.

Acid Phosphatase↗
PubMedDate not supplied

Cardiomyocyte transplantation in a porcine myocardial infarction model.

Transplantation of cardiomyocytes into the heart is a potential treatment for replacing damaged cardiac muscle. To investigate the feasibility and efficiency of this technique, either a cardiac-derived cell line (HL-1 cells), or normal fetal or neonatal pig cardiomyocytes were grafted into a porcine model of myocardial infarction. The myocardial infarction was created by the placement of an embolization coil in the distal portion of the left anterior descending artery in Yorkshire pigs (n = 9). Four to 5 wk after creation of an infarct, the three preparations of cardiomyocytes were grafted, at 1 x 10(6) cells/20 microL into normal and into the middle of the infarcted myocardium. The hearts were harvested and processed for histologic examinations 4 to 5 wk after the cell grafts. Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal pig cardiomyocytes formed stable grafts within the normal myocardium without any detrimental effect including arrhythmia. In addition, a marked increase in angiogenesis was observed both within the grafts and adjacent host myocardium. Electron microscopy studies demonstrated that fetal pig cardiomyocytes and the host myocardial cells were coupled with adherens-type junctions and gap junctions. Histologic examination of graft sites from infarct tissue failed to show the presence of grafted HL-1 cells, fetal, or neonatal pig cardiomyocytes. Cardiomyocyte transplantation may provide the potential means for cell-mediated gene therapy for introduction of therapeutic molecules into the heart.

Animals↗
PubMedDate not supplied

Alcoholism and dementia.

This article reviews epidemiological, neurological, cognitive, and imaging data on alcohol-induced dementia. Recent studies indicate that "heavy alcohol use" (variously defined) is a contributing factor in 21-24% of cases of dementia. Research difficulties include lack of positive diagnostic criteria, few post-mortem studies, and no accepted pathological mechanism. Sulcal widening and ventricular enlargement (occasionally reversible) are the strongest findings in patients with alcohol-induced dementia. There is evidence for peripheral neuropathy, ataxia, sparing of language, and improved prognosis when patients with alcohol-induced dementia are compared to other dements. Case examples, etiologic theories, and recommendations for research, training, and clinical practice are included.

Aged↗
PubMedDate not supplied

Myofibrosarcoma of the head and neck in children.

We have identified a distinctive malignant soft tissue neoplasm that occurred in the head and neck region of six children. Histologically, these neoplasms presented an array of features ranging from low-grade spindle cell to high-grade fibrohistiocytic histologies and often had myoid characteristics. Ultrastructural and immunohistochemical studies indicated that they contained neoplastic myofibroblasts that were variably positive for vimentin (4 positive/4 tested), alpha-smooth muscle actin (4/5), muscle-specific actin (5/5), desmin (2/5), and v-src protein substrate p80/85 (4/5). Three patients died of rapidly progressive unresectable local disease, one died of metastatic and local disease, and two are alive 13 months and 8 years after wide resection. We conclude that these neoplasms form a distinctive subset of pediatric soft tissue sarcomas that display an aggressive clinical behavior, typically with local recurrence, and exhibit features of myofibroblastic differentiation.

Adolescent↗
PubMedDate not supplied

Phospholipase activity in synovial fluid from patients with rheumatoid arthritis, osteoarthritis and crystal-associated arthritis.

Phospholipase activity was assayed in cell-free synovial fluid (SF) from patients with rheumatoid arthritis (RA, n = 28), osteoarthritis (OA, n = 10), and crystal-associated arthritis (C, n = 7) by measuring the release of either [14C]oleic acid or [3H]arachidonic acid from radiolabeled E. coli phospholipids. Activity measured by oleic acid release was not significantly different between the three groups of patients (RA = 571 +/- 43.3, OA = 460 +/- 54.7 and C = 718 +/- 162.6 pmol/min/mg). Arachidonic acid release was significantly (p less than 0.005) less in OA (31 +/- 7.3) than RA (61 +/- 4.7) which was similar to C (58 +/- 17.6 pmol/min/mg). Arachidonic acid release correlated significantly with the SF white blood cell count (r = 0.483, p less than 0.01). This study shows the importance of the type of substrate used to measure phospholipase activity and indicates that differences in the capacity to release arachidonic acid may exist between RA and OA disease states.

Arachidonic Acid↗
PubMedDate not supplied

Alterations in arachidonic acid metabolism and chemotactic response in polymorphonuclear leukocytes from patients with rheumatoid arthritis.

This study examines the interrelationship between arachidonic acid (AA) metabolism and chemotactic potential of human peripheral blood neutrophils from both normal donors and patients with rheumatoid arthritis (RA). We demonstrate that there is a significant inverse relationship between the neutrophil's metabolic capability to produce [3H]LTB4 in response to ionophore A23187 stimulation versus the cell's chemotactic potential to optimal concentrations (i.e., 20 nM) of the chemotactic peptide f-Met-Leu-Phe as determined by leading front (r = 0.567, p = 0.009), mean depth (r = 0.458, p = 0.042), and population ratio (r = 0.471, p = 0.036) analyses. Subsequent Percoll density gradient studies revealed several RA neutrophil subpopulations exhibiting significantly enhanced (p less than 0.05) [3H] AA metabolism over corresponding density normal cells. Based on these results, we speculate that RA peripheral blood neutrophils have been "processed" to become less chemotactically-responsive yet more metabolically-active cells, and that the increased ability to produce LTB4 through both increased phospholipase A2 and lipoxygenase activities are part of the increased metabolic capabilities of the cell.

Arachidonic Acid↗
PubMedDate not supplied

Hospital discharge data used as feedback in planning research and education for primary care.

Are research and training programs in pediatrics, internal medicine, and obstetrics and gynecology (OB-GYN) comprehensive enough to give trainees proficiency in primary care? Controversy exists about which subject areas should be added to the training schema to make them more applicable in primary care. One approach to this controversy is to use the most frequent of serious patient problems that are outside these disciplines as feedback into the process of selecting areas for more comprehensive training. In this study, patients' serious problems were defined as those requiring hospitalization. Diagnoses from the National Hospital Discharge Survey were grouped into categories of morbidity by age and sex. The most frequent categories outside the three disciplines were identified. For pediatrics these problems were trauma, mental disorders, and unintended pregnancy; for internal medicine, trauma, mental and gynecologic disorders, and unintended pregnancy; for OB-GYN, trauma and mental, cardiovascular, pulmonary, gastrointestinal, and arthritic disorders. Since primary care is largely ambulatory care, the next step in the resolution of the controversy would be to define the competency level needed for the prevention, early recognition, and early management of these disorders in the ambulatory care setting. Once defined, competency levels can be examined among trainees in the three specialties, and areas where competency is found inadequate can be emphasized. Although hospitalization data are not the only logical criteria for choosing areas for emphasis, these feedback data offer a method of integrating patients' most frequent severe problems into the selection process.

Adolescent↗