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Biomedical subjects

M P Lynch

Publications and source records attributed to M P Lynch.

At least 19 recordsLinked to original sources
PubMed2005

Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion injury in the rat.

Cervical contusive trauma accounts for the majority, of human spinal cord injury (SCI), yet experimental use of cervical contusion injury models has been limited. Considering that (1) the different ways of injuring the spinal cord (compression, contusion, and transection) induce very different processes of tissue damage and (2) the architecture of the spinal cord is not uniform, it is important to use a model that is more clinically applicable to human SCI. Therefore, in the current study we have developed a rat model of contusive, cervical SCI using the Electromagnetic Spinal Cord Injury Device (ESCID) developed at Ohio State University (OSU) to induce injury by spinal cord displacement. We used the device to perform mild, moderate and severe injuries (0.80, 0.95, and 1.1 mm displacements, respectively) with a single, brief displacement of <20 msec upon the exposed dorsal surface of the C5 cervical spinal cord of female (180-200 g) Fischer rats. Characterization of the model involved the analysis of the temporal histopathological progression of the injury over 9 weeks using histochemical stains to analyze white and gray mater integrity and immunohistochemistry to examine cellular changes and physiological responses within the injured spinal cord. Accompanying the histological analysis was a comprehensive determination of the behavioral functionality of the animals using a battery of motor tests. Characterization of this novel model is presented to enable and encourage its future use in the design and experimental testing of therapeutic strategies that may be used for human SCI.

Animals↗
PubMed2004

BAG-1 expression in normal and neoplastic endometrium.

OBJECTIVE: BAG-1 has anti-apoptotic actions and is known to bind BCL-2 and steroid receptors. High levels of BAG-1 have been implicated as a prognostic indicator in breast cancer. Whether this observation can be generalized to endometrial cancer remains unknown. METHODS: IRB permission was obtained for use of human discarded tissue. Immunohistochemical analyses were performed on: proliferative endometrium (PEM, 6), secretory endometrium (SEM, 28), "low-grade" neoplastic lesions (complex atypical hyperplasia and grade 1 endometrial adenocarcinomas) (19), and "high-grade" cancers (grade 2 and 3 endometrial adenocarcinomas) (13). The level of total BAG-1 and its isoforms was evaluated by Western blot in lysates from Ishikawa cells (grade 1), MFE 296 cells (grade 2), and SK-UT(2) cells (grade 3). RESULTS: The proportion of "high-grade" cancers with positive cytoplasmic staining for BAG-1 was higher than that of secretory endometrium (P = 0.006). Additionally, the proportion of specimens with positive staining for nuclear BAG-1 expression was significantly higher among high-grade carcinoma specimens compared to secretory specimens (P = 0.009). A high proportion (91%) of all specimens were positive for BCL-2, limiting the ability to subcategorize the other variables analyzed. There was no relationship between positive nuclear BAG-1 expression and either estrogen receptor (ER) or progesterone receptor (PR) expression. BAG-1 was expressed in the three cell lines evaluated and total BAG-1 level was not different among the different cell lines. CONCLUSION: BAG-1 is expressed in the endometrium. High-grade cancers stain more frequently than secretory endometrium for both cytoplasmic and nuclear BAG-1 expression, perhaps indicating an association between expression of BAG-1 and prognosis.

Adenocarcinoma↗
PubMed2003

The effect of treating alfalfa with Lactobacillus buchneri 40788 on silage fermentation, aerobic stability, and nutritive value for lactating dairy cows.

Lactobacillus buchneri 40788 and enzymes (beta-glucanase, alpha-amylase, xylanase, and galactomannase) were applied to chopped alfalfa (39% DM) to study their effects on the fermentation and nutritive value of the silage. Alfalfa was treated with nothing, or L. buchneri 40788, for a final application rate of 1 x 10(5), 5 x 10(5), or 1 x 10(6) cfu/g of fresh forage and ensiled in laboratory silos for 2, 4, 8, and 56 d. Treatment with L. buchneri 40788 had few effects on the end products of fermentation through 8 d of ensiling. However, after 56 d of ensiling, treated silages had a higher pH (4.55 vs. 4.38) and higher concentrations of acetic acid (6.40 vs. 4.24%), propionic acid (0.18 vs. 0.06%), and ammonia-N (0.35 vs. 0.29%) when compared to untreated silage. Lactic acid was also numerically lower in treated (3.51%) than untreated (4.12%). Silages treated with the moderate and highest dose of L. buchneri 40788 also resulted in greater recoveries of DM than did untreated silage. Alfalfa (43% DM) was also untreated or treated with a commercial application of L. buchneri 40788 (4 x 10(5) cfu/g, a commercial dose) in farm-scale bag silo. Holstein cows were fed a diet comprised of 32% untreated or treated alfalfa silage, 11% corn silage, 5% chopped alfalfa hay, and 52% of concentrate (DMB) for a 6-wk treatment period. Dry matter intake and milk composition were unaffected by treatment, but cows fed silage treated with L. buchneri 40788 produced 0.8 kg more milk than did cows fed untreated silage. Treated silage had a higher concentration of acetic acid (5.67 vs. 3.35%) but lower lactic acid (3.50 vs. 4.39%) than untreated silage. When exposed to air, the total mixed ration containing treated alfalfa silage remained stable for 100 h, whereas the ration containing untreated silage spoiled after 68 h. Treating alfalfa silage with L. buchneri 40788 increased the concentration of acetic acid, and when the silage was combined into a total mixed ration and fed to lactating cows, it improved the aerobic stability of the ration and increased milk production.

Acetic Acid↗
PubMed2002

Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients with rheumatoid arthritis: a prospective study incorporating HRCT scanning and pulmonary function tests.

OBJECTIVE: Methotrexate has a well-recognized side-effect of acute hypersensitivity pneumonitis. There is concern about whether chronic pulmonary toxicity can occur with methotrexate treatment. Our objective was to compare chest high-resolution computed tomography (HRCT) findings and serial pulmonary function tests in rheumatoid arthritis (RA) patients on methotrexate with findings for a control group of patients with RA who were not being treated with methotrexate. METHODS: Study patients had an initial chest radiograph, full pulmonary function tests and chest HRCT. Pulmonary function tests were then performed regularly over a 2-yr period. RESULTS: Fifty-five RA patients on methotrexate and 73 control patients with RA were enrolled for the study. Mean dose of methotrexate was 10.7 mg/week (S.D. 2.5 mg/week) and mean duration of treatment at entry into the study was 30 (20) months. Twenty per cent of patients with RA treated with methotrexate had pulmonary fibrosis (PF) on initial HRCT compared with 23% in the control group. When the patients with and without PF were compared, there was no statistical difference in the duration (mean difference -4.18 months, P=0.237) or dose (mean difference -0.8 mg/week P=0.52) of methotrexate therapy. Mean changes after 2 yr in forced expiratory volume, forced vital capacity, diffusion capacity for carbon monoxide and residual volumes were not different in the methotrexate group compared with the control group. CONCLUSION: There is no evidence to suggest clinically, from HRCT assessment or serial pulmonary function tests, that low-dose methotrexate is associated with chronic interstitial lung disease.

Administration, Oral↗
PubMed2002

Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis.

BACKGROUND: Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra-articular feature of rheumatoid arthritis (RA). Features that predict progression of FA in patients with RA have not yet been determined. OBJECTIVE: To identify clinical features that predict progressive FA in patients with RA. METHODS: An unselected cohort of 29 patients with RA and FA confirmed by high resolution computed tomography (HRCT) were studied prospectively for 24 months. Three monthly clinical assessment, four monthly pulmonary function tests, and yearly HRCT scanning was undertaken on these patients. Progressive FA was defined as >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing FA on HRCT or death as a result of FA. RESULTS: During 24 months of follow up 10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute ground glass exacerbations or increasing reticular pattern lung involvement. Progressive FA was associated with the presence of bibasal crackles (p=0.041), TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung involvement on HRCT at initial presentation. When multiple logistic regression was used, only TLCO remained significant. Receiver operator curve analysis was employed to identify presenting TLCO of progressive FA. A TLCO <54% of the predicted value demonstrated 80% sensitivity and 93% specificity in predicting progressive FA. CONCLUSIONS: A TLCO <54% of the predicted value is a highly specific predictor of disease progression.

Aged↗
PubMed2001

Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA.

OBJECTIVES: To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease. METHODS: 239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset. RESULTS: An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003). CONCLUSIONS: Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.

Adult↗
PubMed2001

Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests.

BACKGROUND: Fibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA). Before the availability of high resolution computed tomographic (HRCT) scanning, it was difficult to diagnose accurately without recourse to biopsy. Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19-44%. The term ILD used by these authors encompasses a variety of appearances on HRCT scans. This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics. METHODS: One hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease. All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests. RESULTS: Seventy percent of patients were current or reformed cigarette smokers. Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae. None of the previously suggested risk factors for developing FA were confirmed. Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (TLCO), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA. CONCLUSIONS: HRCT evidence of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.

Aged↗
PubMed2001

Development of a home-based family caregiver cancer education program.

INTRODUCTION: This article describes a home-based educational program developed specifically for family caregivers of cancer patients who receive hospice and home care. The overall aim of this educational program is to specifically address family caregivers' needs for acquisition of necessary knowledge and skills to meet the physical and psychosocial demands associated with caring for a patient with advanced cancer. PROGRAM DEVELOPMENT: Originally, components of this program were offered in a small group discussion format within hospital and community settings. The educational program was transformed to accommodate the unique needs and constraints of homebound family caregivers who have very limited time and/or opportunities for support and education outside of the home. The program is comprised of educational modules that provide hospice and home care professionals with written and audiovisual materials designed to facilitate brief, structured, educational encounters with family caregivers in the home setting. DISCUSSION: Two hundred thirty-seven educational module kits were distributed to professionals affiliated with twenty-four home care and hospice agencies in the Greater Philadelphia area. Results of a telephone survey designed to elicit evaluation data from professional staff members who had used the educational modules are presented. Limitations, plans for future program evaluation, cost implications, and implementation recommendations related to this educational program are described.

Caregivers↗
PubMed2000

Effect of aldehyde lipid oxidation products on myoglobin.

The effects of aldehyde lipid oxidation products on myoglobin (Mb) were investigated at 37 degrees C and pH 7.2. Oxymyoglobin (OxyMb) oxidation increased in the presence of 4-hydroxynonenal (4-HNE) compared to controls (P < 0.05). Preincubation of metmyoglobin (MetMb) with aldehydes rendered the heme protein a poorer substrate for enzymatic MetMb reduction compared to controls, and the effect was inversely proportional to preincubation time; unsaturated aldehydes were more effective than saturated aldehydes (P < 0.05). The order of MetMb reduction as affected by preincubation was control > hexanal > heptanal > octanal > nonanal = decanal = hexenal > heptenal = octenal > nonenal = decenal = 4-HNE (P < 0.05). Preincubation of MetMb with 4-HNE enhanced the subsequent ability of the heme protein to act as a prooxidant in both liposomes and microsomes when compared to controls (P < 0.05); the effect was reduced in microsomes containing elevated concentrations of alpha-tocopherol (P < 0.05). MetMb preincubation with mono-unsaturated aldehydes enhanced the catalytic activity of MetMb to a greater degree than saturated aldehydes (P < 0.05). These results suggest that aldehyde lipid oxidation products can alter Mb stability by increasing OxyMb oxidation, decreasing the ability of MetMb to be enzymatically reduced and enhancing the prooxidant activity of MetMb.

Aldehydes↗
PubMed2000

Raised pulmonary artery pressures measured with Doppler echocardiography in rheumatoid arthritis patients.

OBJECTIVE: To study the prevalence of echocardiographic abnormality and pulmonary hypertension in an unselected population of patients with rheumatoid arthritis (RA). METHOD: One hundred and forty-six RA patients, irrespective of cardiopulmonary symptoms, were assessed clinically and by echocardiography, including pulmonary artery pressure measurement, ECG, pulmonary function tests and high-resolution computed tomography scanning of the thorax. RESULTS: Two-dimensional echocardiography demonstrated significant cardiac disease in the form of reduced left ventricular ejection fraction (<64%) in 9% of patients, moderate mitral regurgitation in 4%, aortic stenosis in 4%, aortic regurgitation in 3% and Valsalva sinus rupture in 0.7%. In addition, 1% had detectable pericardial effusions. Thirty-one per cent of the RA patients had an estimated pulmonary artery systolic pressure of 30 mmHg or more, and 21% of all the RA patients had pulmonary hypertension without significant cardiac disease or lung disease evident on pulmonary function testing. CONCLUSIONS: A wide and frequent variety of echocardiographic cardiac abnormalities may be found in an unselected population of patients with RA. Using Doppler echocardiography, we have found pulmonary hypertension secondary to lung disease in 6% of the population and a larger than expected prevalence of mild primary pulmonary hypertension in patients with RA. The latter observation may be relevant to the high incidence of cardiovascular-related deaths observed in patients with RA

Adult↗
PubMed1998

Apoptosis during bone-like tissue development in vitro.

We present evidence of cell death by apoptosis during the development of bone-like tissue formation in vitro. Fetal rat calvaria-derived osteoblasts differentiate in vitro, progressing through three stages of maturation: a proliferation period, a matrix maturation period when growth is downregulated and expression of the bone cell phenotype is induced, and a third mineralization stage marked by the expression of bone-specific genes. Here we show for the first time that cells differentiating to the mature bone cell phenotype undergo programmed cell death and express genes regulating apoptosis. Culture conditions that modify expression of the osteoblast phenotype simultaneously modify the incidence of apoptosis. Cell death by apoptosis is directly demonstrated by visualization of degraded DNA into oligonucleosomal fragments after gel electrophoresis. Bcl-XL, an inhibitor of apoptosis, and Bax, which can accelerate apoptosis, are expressed at maximal levels 24 h after initial isolation of the cells and again after day 25 in heavily mineralized bone tissue nodules. Bcl-2 is expressed in a reciprocal manner to its related gene product Bcl-XL with the highest levels observed during the early post-proliferative stages of osteoblast maturation. Expression of p53, c-fos, and the interferon regulatory factors IRF-1 and IRF-2, but not cdc2 or cdk, were also induced in mineralized bone nodules. The upregulation of Msx-2 in association with apoptosis is consistent with its in vivo expression during embryogenesis in areas that will undergo programmed cell death. We propose that cell death by apoptosis is a fundamental component of osteoblast differentiation that contributes to maintaining tissue organization.

Animals↗