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Biomedical subjects

M Logue

Publications and source records attributed to M Logue.

14 recordsLinked to original sources

Stability of hibernating myocardium in pigs with a chronic left anterior descending coronary artery stenosis: absence of progressive fibrosis in the setting of stable reductions in flow, function and coronary flow reserve.

OBJECTIVES: This study was performed to determine whether hibernating myocardium is adaptive or is destined to undergo progressive irreversible injury. BACKGROUND: Previous studies have suggested that hibernating myocardium eventually results in progressive dysfunction. Since serial studies cannot be performed in humans, the temporal progression of physiologic and structural adaptations was evaluated in pigs with hibernating myocardium. METHODS: Pigs were instrumented with a left anterior descending coronary artery (LAD) stenosis (1.5 mm) and underwent physiologic studies three to five months later to quantify regional function, perfusion and 18F-2-deoxyglucose (FDG) uptake. Viability was confirmed by histology and contractile reserve. RESULTS: Hibernating myocardium was characterized by severe regional dysfunction (centerline score, -1.9+/-0.1), reduced resting subendocardial flow (LAD: 0.85+/-0.03 vs. normal: 1.02+/-0.03 ml/min/g, p < 0.01), critically reduced subendocardial flow reserve (adenosine flow: 1.04+/-0.09 ml/min/g, p = NS vs. rest; epinephrine flow: 0.88+/-0.07 ml/min/g, p = NS vs. rest) and increased FDG uptake (0.022+/-0.002 vs. 0.014+/-0.001 ml/g/min, p < 0.01). Physiologic parameters were not different among animals studied at three (93+/-1 days, n = 27), four (118+/-2 days, n = 26) or five months (150+/-6 days, n = 9). Pathology revealed a small increase in LAD connective tissue (6.4+/-0.4% vs. 4.0+/-0.2%, p < 0.001), with no change over this time frame. CONCLUSIONS: Thus, physiologic and structural features of hibernating myocardium remain constant for at least two months. The absence of functional deterioration or progressive fibrosis suggests that hibernation is adaptive rather than an unstable physiology destined to progress to irreversible injury. The stability of this model appears ideally suited for interventions targeted to improve flow and function in chronically dysfunctional myocardium.

Animals↗

Combined multipoint analysis of multiple asthma data sets based on the posterior probability of linkage.

In the presence of multiple data sets, an important issue is how to best measure the overall evidence for linkage across data sets. Previously, we advocated the use of the posterior probability of linkage (PPL) for this purpose [Vieland, Am J Hum Genet 63:947-54, 1998; Wang et al., Ann Hum Genet 64:533-53, 2000; Vieland et al., Hum Hered 51:199-208, 2001]. In this paper, we propose a critical modification of our earlier two-point PPL in order to handle multiple-point calculations. The proposed modification is then applied to the genome-screen data sets and the COAG chromosome 5 data sets provided by GAW 12. We find linkage signals at location (in the order of the strength of the signal) 45 cM on chromosome 6, 23 cM on chromosome 20, and 30 cM on chromosome 1. No linkage signal is found on chromosome 5.

Adult↗

A prospective randomised trial to compare the efficacy and safety of hemabate and syntometrine for the prevention of primary postpartum haemorrhage.

In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.

Adult↗

Prediction of mandibular growth rotation: assessment of the Skieller, Björk, and Linde-Hansen method.

The purpose of this investigation was to assess the method proposed by Skieller, Björk, and Linde-Hansen in 1984 to predict mandibular growth rotation. Our sample consisted of 40 randomly selected, untreated, adolescent subjects representative of the patient population generally encountered in orthodontic practice. The four independent variables identified in the Skieller study as having the highest predictive value (mandibular inclination, intermolar angle, shape of the lower border of the mandible, and inclination of the symphysis) were identified on initial lateral cephalograms. The proposed regression equations were applied and predicted mandibular rotations obtained. Final lateral cephalograms made 6 years after the initial profile radiographs were superimposed and actual mandibular rotation recorded. The observed and predicted rotations were compared and regression analyses performed to determine the amount of variability in observed values accounted for by the four variables individually and in combination. Only 5.6% of the variability in mandibular growth rotation could be accounted for using the four variables individually. Only 9% of the variability could be accounted for with a combination of the variables. In addition, we performed a Monte Carlo analysis, which mirrored the Skieller analysis but used random numbers instead of actual cephalometric data, to determine if the Skieller results may simply have capitalized on chance. Using the same forward stepwise selection procedure with a rejection level of P >.1, we found after 5000 simulations that a mean of 84% and a median of 94% of mandibular growth rotation variability could be accounted for using meaningless data in the Skieller analysis. This result was comparable to the Skieller value of 86%. In conclusion, information derived from pretreatment lateral cephalograms using the Skieller, Björk, and Linde-Hansen method does not permit clinically useful predictions to be made in a general population relative to the direction of future mandibular growth rotation.

Cephalometry↗

Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer's disease but not of Down's syndrome patients.

Concentrations of glycerophosphocholine and of glycerophosphoethanolamine, the metabolites of two major membrane phospholipid classes, phosphatidylcholine and phosphatidylethanolamine respectively, were determined post-mortem in cortical areas 20 and 40 and in cerebellum and caudate nucleus of brains obtained at autopsy from patients with Alzheimer's disease, Down's syndrome and age-matched control subjects. Glycerophosphocholine concentrations in all of the brain regions examined were higher by 67-150% in Alzheimer's disease than in control brains and 81-104% higher in Alzheimer's disease than in Down's syndrome. Glycerophosphoethanolamine concentrations were 21-52% higher in Alzheimer's disease than in controls, and 27-92% higher in Alzheimer's disease than Down's syndrome. Levels of glycerophosphocholine and of glycerophosphoethanolamine did not differ significantly between Down's syndrome and control brains. These data indicate that abnormal phospholipid metabolism in brain is characteristic of Alzheimer's disease but not Down's syndrome and suggest that this abnormality may be a central pathophysiological feature of Alzheimer's disease because levels of glycerophosphocholine and of glycerophosphoethanolamine are elevated in brain regions with and without manifestations of histopathology.

Aged↗

Effects of running the Boston marathon on plasma concentrations of large neutral amino acids.

Plasma large neutral amino acid concentrations were measured in thirty-seven subjects before and after completing the Boston Marathon. Concentrations of tyrosine, phenylalanine, and methionine increased, as did their "plasma ratios" (i.e., the ratio of each amino acid's concentration to the summed plasma concentrations of the other large neutral amino acids which compete with it for brain uptake). No changes were noted in the plasma concentrations of tryptophan, leucine, isoleucine, nor valine; however, the "plasma ratios" of acid patterns may influence neurotransmitter synthesis.

Amino Acids↗

Perineal muscle function after childbirth.

Perineal muscle function was measured in a group of European women 1 year after childbirth by means of a perineometer. There was no correlation between the degree of perineal trauma and subsequent muscle function. The efficiency of the perineal muscles was found to be significantly related to the extent to which women took regular exercise.

Episiotomy↗

CSF monoamine metabolite levels in Alzheimer's and Parkinson's disease.

Levels of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in lumbar CSF from 32 patients with a clinical diagnosis of Alzheimer's disease (AD) and from 21 patients with Parkinson's disease (PD). The baseline CSF metabolite values did not differ significantly between the two groups of patients, although HVA levels were lowest in patients with PD and in the more severely demented patients with AD. Levels of all three metabolites increased significantly in both patient groups during probenecid administration, but HVA levels were significantly higher in patients with AD than in patients with PD. Within the AD group, those with the most severe dementia had the greatest rise in MHPG levels. Alterations in monoamine metabolite levels in the CSF detected during probenecid administration aid in the differential diagnosis of neurodegenerative diseases such as AD.

Adult↗

Effects of oral L-tyrosine administration on CSF tyrosine and homovanillic acid levels in patients with Parkinson's disease.

To determine whether 1-tyrosine administration can enhance dopamine synthesis in humans as it does in rats, we measured levels of tyrosine and the major dopamine metabolite, homovanillic acid, in lumbar spinal fluids of 23 patients with Parkinson's disease before and during ingestion of 100 mg/kg/day of tyrosine. Nine patients took 100 mg/kg/day of probenecid in six divided doses for 24 hours prior to each spinal tap; 14 patients did not receive probenecid. L-tyrosine administration significantly increased CSF tyrosine levels in both groups of patients (p less than .01) and significantly increased homovanillic acid levels in the group of patients pretreated with probenecid (p less than .02). These data indicate that l-tyrosine administration can increase dopamine turnover in patients with disorders in which physicians wish to enhance dopaminergic neurotransmission.

Administration, Oral↗

Normal plasma choline responses to ingested lecithin.

We examined plasma choline changes after ingestion of diets composed of common foodstuffs, with choline contents bracketing the average daily intake in the American diet, and ingestion of diets supplemented with exogenous purified lecithin. A diet with low choline content did not increase plasma choline concentrations; a diet with high choline content doubled plasma choline levels. A lecithin-supplemented (25 gm; 80% phosphatidylcholine) low-choline diet increased plasma choline levels 400%. These findings indicate that normal diets cause only small elevations in plasma choline; purified lecithin supplements are likely to have greater effects in treating neurologic diseases.

Adolescent↗

Lymphocyte surface modulation and cyclic nucleotides I. Topographic correlation of cyclic adenosine 3':5'-monophosphate and immunoglobulin immunofluorescence during lymphocyte capping.

The cross-linking of human peripheral lymphocyte surface Ig results in an early association of cyclic adenosine 3':5'-monophosphate (cAMP) and the cell surface Ig patches. Examination of the subsequent stages of cap formation reveals the continued relationship of cAMP and the clustered surface Ig. In addition, the generalized influx of calcium produced by the ionophore A-23187 disrupts human lymphocyte caps. During the process of cap dissolution cAMP is still associated with surface Ig. Therefore, it is hypothesized that the localized concentration of cyclic nucleotide and calcium ion regulates the movement of cell surface constituents by coordinating the function of the cell's contractile and structural elements.

Calcimycin↗

Subpopulations of human lymphoblastoid cell lines. Correlation with the expression of surface receptors and content of Epstein-Barr virus genome.

Forty lymphoblast cell lines derived from normal subjects, patients with infectious mononucleosis, leukemia, and Burkitt's lymphoma have been studied for surface receptors including surface Ig, complement receptors by the EAC rosette and fluorescent (Raji cell) techniques, and Fc (aggregate) receptor by direct and indirect immunofluorescence. Because of the B-cell tropism of the Epstein-Barr virus (EBV), an effort was made to correlate the expresion of various surface properties of lymphoblastoid cell lines with the content of EBV viral DNA as determined by complementary RNA-DNA (cNRA-DNA) hybridization on membrane filters or by DNA-DNA renaturation kinetic analysis. The only correlation established was with the Fc receptor determined by direct immunofluorescence. No correlation of EBV genome equivalents per cell with complement receptor or surface Ig was noted, suggesting that the expression of these receptors is not influenced by EBV viral DNA content. Subgroups of lymphoblastoid cell lines were on the basis of variable expression of surface receptors, designated B1, B2, B3, B4, and T. The distribution of lymphoblastoid cell lines into these subgroups were in the ratio of 14:4:1:4:1. The B1, B2, and B4 cell lines (except Molt 4F) were found to contain EBV. The B3 subgroup, for wich cell line 698 was the sole example, expressed surface immunoglobulins but no other B-cell characteristics, and H.S.B., a T-cell line, lacked detectable EBV.

Burkitt Lymphoma↗