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Biomedical subjects

M J Cunningham

Publications and source records attributed to M J Cunningham.

At least 91 records · Page 5Linked to original sources
PubMed1990

Influence of glucose and insulin on the exaggerated diastolic and systolic dysfunction of hypertrophied rat hearts during hypoxia.

Myocardial hypertrophy can result in increased sensitivity toward the development of mechanical dysfunction during hypoxia. Alterations in glycolytic metabolism may contribute to this. We studied the response to 15 minutes of hypoxia in hypertrophied (deoxycorticosterone-salt hypertension model) and nonhypertrophied rat hearts and examined the influence of a high glucose (27.5 mM) and insulin (100 mU/ml) concentration. In response to hypoxia in the presence of a normal glucose concentration (5.5 mM), left ventricular end-diastolic pressure was higher in hypertrophied than in nonhypertrophied hearts (65 +/- 6 vs. 44 +/- 4 mm Hg; p less than 0.05). Perfusion with high glucose and insulin blunted the rise in left ventricular end-diastolic pressure in both hypertrophied and nonhypertrophied hearts and abolished the difference in diastolic dysfunction between groups during hypoxia (26 +/- 2 vs. 32 +/- 4 mm Hg, respectively; p = NS). At end hypoxia in the presence of a normal glucose concentration, developed pressure was more depressed in hypertrophied than in nonhypertrophied hearts (11 +/- 1 vs. 18 +/- 1% of baseline, respectively; p less than 0.05). Perfusion with high glucose and insulin resulted in improved function in both groups during hypoxia such that a greater impairment of developed pressure was no longer present in the hypertrophied versus nonhypertrophied hearts (21 +/- 1 vs. 24 +/- 2% of baseline, respectively; p = NS). At the end of hypoxic perfusion in the presence of a normal glucose concentration, hypertrophied hearts were producing 38% less lactate than nonhypertrophied hearts. Perfusion with high glucose and insulin increased lactate production in both groups and equalized lactate production between groups. Thus, the greater deterioration in hemodynamic function in hypertrophied hearts compared with nonhypertrophied hearts during hypoxia is associated with lower lactate production. Both the exaggerated hemodynamic dysfunction and deficient lactate production can be ameliorated by perfusion with a high glucose concentration and insulin.

Animals↗
PubMed1990

Contribution of endothelial cells to calcium-dependent fluorescence transients in rabbit hearts loaded with indo 1.

In studies that attempt to measure intracellular calcium [( Ca2+]i) in the intact heart with the calcium indicator indo 1-AM, a fundamental assumption is that the signals report changes in myocyte [Ca2+]i. We studied isolated perfused rabbit hearts loaded with the calcium probe indo 1-AM and recorded surface fluorescence of the left ventricle during continuous excitation at 360 nm. In cells containing indo 1, an increase in [Ca2+]i is associated with an increase in fluorescence intensity at 400 nm, a decrease in intensity at 500 nm, and an increase in the 400:500 nm ratio. Beat-to-beat fluorescence transients were recorded from the surface of the heart coincident with contraction, indicating that a component of the fluorescence signals is derived from beating myocytes. To evaluate the potential contribution of endothelial cells, we compared the response to increases in [Ca2+]o or bradykinin (10(-5) M). In response to an increase of the [Ca2+] in the perfusate from 0.6 to 3.0 mM, left ventricular developed pressure and +dP/dt increased with a simultaneous increase in the [Ca2+]i-sensitive 400:500 nm ratio. Perfusion with the endothelial cell agonist bradykinin caused no change in left ventricular isovolumic peak systolic pressure or left ventricular dP/dt, whereas bradykinin evoked an immediate elevation in both the diastolic and systolic levels of the [Ca2+]i-sensitive 400:500 nm ratio. In additional experiments with indo 1-loaded isolated beating myocytes, superfusion with bradykinin had no effect on either the fluorescence [Ca2+]i transients or contractility. In contrast, superfusion of indo 1-loaded cultured endothelial cells with bradykinin caused the elevation of [Ca2+]i within seconds. Fluorescence microscopy of unstained frozen tissue sections from indo 1-loaded hearts also suggested the presence of more intense microvascular endothelial cell indo 1 fluorescence relative to that observed in myocytes. These experiments provide evidence that a component of [Ca2+]i-sensitive fluorescence of whole hearts loaded with indo 1 is contributed by nonmyocyte sources, including endothelial cells. These results also raise the caution that the abrupt rise of [Ca2+]i that has been observed during the initial phase of ischemia in whole hearts loaded with indo 1 may be partly derived from endothelial cells rather than myocytes.

Animals↗
PubMed1990

In vitro and in vivo genotoxicity of 1,3-butadiene and metabolites.

1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange (SCE) and micronucleus induction results indicated 1,3-butadiene was genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats to 1,3-butadiene carcinogenicity. However, 1,3-butadiene did not induce unscheduled DNA synthesis (UDS) in the rat or mouse hepatocytes following in vivo exposure. Likewise, UDS in rat and mouse hepatocytes in vitro was not induced by EB or DEB. Salmonella typhimurium gene mutation (Ames) tests of 1,3-butadiene using strains TA1535, TA97, TA98, and TA100 and employing rat, mouse, and human liver S9 metabolic systems were barely 2-fold above background only in strain TA1535 at 30% 1,3-butadiene in air with induced and uninduced rat S9 and mouse S9 (uninduced). 1,3-Butadiene was negative in in vitro SCE studies in human whole blood lymphocytes cultures treated in the presence of rat, mouse, or human liver S9 metabolic activation. In general, 1,3-butadiene is genotoxic in vivo but is a weak in vitro genotoxin.

Animals↗
PubMed1989

Otologic manifestations of Langerhans' cell histiocytosis.

Eighteen of 62 children diagnosed with Langerhans' cell histiocytosis at the Children's Hospital of Pittsburgh (Pa) between 1970 and 1986 demonstrated ear and temporal bone involvement. In six children, such otologic disease was their sole presenting manifestation. Common signs and symptoms included aural discharge, postauricular swelling, and conductive hearing loss. The otologic findings in these children, if not investigated properly, could easily be attributed to acute or chronic infectious ear disease. Computed tomography with contrast enhancement proved to be particularly valuable as a diagnostic study because of its clear delineation of both osseous and soft-tissue temporal bone involvement. Computed tomographic findings could also be used to enhance local treatment by guiding surgical biopsy and curettage procedures or defining low-dose radiation therapy portals. Eleven of these 18 children with otologic Langerhans' cell histiocytosis additionally required chemotherapy due to the systemic nature of their disease.

Child↗
PubMed1989

Metabolism and binding of benzo[a]pyrene in randomly-proliferating, confluent and S-phase human skin fibroblasts.

The metabolism of benzo[a]pyrene in randomly proliferating and confluent cultures of human skin fibroblast cells was compared with cell cultures in early S phase of the cell cycle after a G1 block. When each cell population was exposed to [G-3H]benzo[a]pyrene for 24 hours and the organic soluble metabolites in the extracellular medium and intracellular components were analyzed by HPLC, a quantitative increase in metabolism was observed in the confluent cell populations. The amount of organic soluble metabolites in the extracellular medium of the confluent dense cultures was 2.7 times the amount found in randomly proliferating cultures and 1.5 times that of the synchronized cultures. The trans-7,8- and 9,10 dihydrodiols and 3-hydroxy benzo[a]pyrene were the major metabolites formed. Small amounts of the sulphate conjugate, 9-hydroxy-benzo[a]pyrene and the tetrols were also detected. Cytoplasmic as well as nuclear extracts from the confluent cell cultures also contained higher amounts of metabolites compared to those from the randomly proliferating and S-phase cells. The levels of DNA modification by metabolically activated benzo[a]pyrene did not differ among the randomly proliferating, confluent and S-phase cells. However, the S-phase cells exhibited approximately 50-fold increase in the frequency of transformation compared to the randomly proliferating cells. Confluent cells were not transformed by benzo[a]pyrene. These data suggest that factors other than random modification of DNA by the carcinogen might have a significant role in the expression of a transformed phenotype and that metabolism and transformation are not directly related. Furthermore, confluent dense cultures with a heightened capability for metabolism of benzo[a]pyrene were more active in the detoxification of benzo[a]pyrene than in the production of the metabolites associated with cellular transformation.

Benzo(a)pyrene↗
PubMed1989

SDS-PAGE protein patterns of yeasts from human sources.

Protein patterns of Candida species and other yeasts have been studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Although differences in patterns occur which tend to separate the species, variability between replicate samples is sometimes high. The method cannot be used for speciation of common yeasts from medical sources.

Candida↗
PubMed1989

Deleterious effect of ouabain on myocardial function during hypoxia.

The effect of cardiac glycosides on myocardial function during hypoxia is controversial. Accordingly, we studied left ventricular performance during hypoxia and reoxygenation in the presence of a mildly inotropic, nontoxic dose of ouabain using isolated, isovolumic, buffer-perfused rabbit hearts. After 15 min of hypoxia, left ventricular developed pressure was less in the ouabain-treated group than in controls (35 +/- 4 vs. 55 +/- 3 mmHg, P less than 0.025). Left ventricular end-diastolic pressure (LVEDP) increased more during hypoxia in the presence of ouabain (9 +/- 1 to 32 +/- 7 with ouabain vs. 9 +/- 1 to 14 +/- 3 mmHg without ouabain, P less than 0.005) despite comparable degrees of coronary vasodilatation and myocardial lactate production in the two groups. When coronary flow was abruptly reduced to zero to eliminate the coronary turgor contribution to diastolic pressure, LVEDP after 15 min of hypoxia in the presence of ouabain was greater than that in control hearts that did not receive ouabain (13 +/- 4 vs. 4 +/- 1 mmHg, P less than 0.05), implicating greater diastolic myocardial fiber tension in the ouabain group during hypoxia. With reoxygenation, recovery of developed pressure was less and end-diastolic pressure remained elevated in the ouabain-treated group when compared with controls. We conclude that a modestly inotropic dose of ouabain exacerbates the decrease in diastolic ventricular distensibility induced by hypoxia, worsens the decline in developed pressure during hypoxia, and impairs recovery during reoxygenation.

Animals↗
PubMed1989

Progressive improvement in pulmonary vascular resistance after percutaneous mitral valvuloplasty.

Percutaneous mitral valvuloplasty has been proposed as a nonsurgical technique for treating high-risk patients with mitral stenosis who are deferred from mitral valve replacement. The effect of this technique on patients with pulmonary hypertension, however, has not been fully evaluated. Accordingly, serial assessment of pulmonary vascular resistance was made in 14 patients with critical mitral stenosis and pulmonary hypertension (pulmonary vascular resistance greater than 250 dynes.sec/cm5 or mean pulmonary artery pressure greater than 40 mm Hg or both) who underwent percutaneous balloon dilatation of the mitral valve. Balloon valvuloplasty was performed with either one (n = 10) or two (n = 4) balloons through the transseptal approach, and it resulted in significant improvement in mean mitral gradient (from 18 +/- 4 to 9 +/- 4 mm Hg, p less than 0.001), systemic blood flow (from 3.7 +/- 1.2 to 5.0 +/- 2.2 l/min, p less than 0.001), and calculated mitral valve area (from 0.7 +/- 0.2 to 1.6 +/- 0.7 cm2, p less than 0.001). Immediately after balloon mitral valvuloplasty, pulmonary vascular resistance fell from 630 +/- 570 to 447 +/- 324 dynes.sec/cm5. Repeat catheterization 7 +/- 4 months after valvuloplasty showed further improvement of pulmonary hypertension in 12 of the 14 patients, with a mean pulmonary vascular resistance for the group as a whole of 280 +/- 183 dynes.sec/cm5, p less than 0.005. In two patients, mitral valve restenosis to a mitral valve area less than 1.0 cm2 was associated with a return of pulmonary hypertension to predilatation values.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Balloon aortic valvuloplasty in 170 consecutive patients.

Between October 1, 1985, and April 1, 1988, we performed balloon aortic valvuloplasty in 170 patients (mean age [+/- SD], 77 +/- 5 years) who had symptomatic aortic stenosis. The procedure was completed successfully in 168 patients and resulted in significant increases in the mean (+/- SD) aortic-valve area (from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2) and cardiac output (from 4.6 +/- 3.4 to 4.8 +/- 1.4 liters per minute) and decreases in the peak aortic-valve pressure gradient (from 71 +/- 20 to 36 +/- 14 mm Hg) (P less than 0.01 for all three comparisons). There were six in-hospital deaths, and five patients required early aortic-valve replacement. Follow-up data were available for all patients, for a period averaging 9.1 months. In addition to the 6 patients who died in the hospital, 25 patients died an average of 6.4 +/- 5.3 months after discharge. Symptoms recurred in 44 patients; they were managed by repeat valvuloplasty in 16 patients, by aortic-valve replacement in 17, and by medical therapy in 11. At the most recent follow-up examination, the symptoms of 103 patients had improved after valvuloplasty; this number includes 15 patients with restenosis who successfully underwent redilation. Life-table analysis indicates that the probability of survival 12 months after the procedure was 74 percent. We conclude that balloon aortic valvuloplasty is an effective palliative therapy for some elderly patients with symptomatic aortic stenosis. Symptoms improve in the majority of patients; although restenosis is common, it can be managed in some patients by repeat balloon dilation.

Adult↗
PubMed1988

Evaluation of noninvasive eustachian tube function tests in normal adults.

A causal association between eustachian tube (ET) dysfunction and otitis media (OM) has been documented. We present normative data for eustachian tube function (ETF) in an otologically normal population of 107 college-age subjects using two noninvasive methods: nine-step tympanometric testing and sonotubometry. The results show a 78% agreement between the two methods when one test session was performed. The nine-step test showed a 52% repeatability rate on three sequential test sessions while the sonotubometry test showed a 34% repeatability rate. The combined tests showed a 34% agreement for the three sequential tests. The findings reveal that the combination of the two tests identify 96% of normal subjects as having at least some tubal function present. Although both tests provide similar information regarding the presence of tubal opening, the sonotubometry method is more physiologic. Additional information shows that the average category of the nine-step test in a normal population was category 2, the mean duration of tubal dilation was 0.40 seconds, and the mean middle-ear pressure was -12 mm H2O.

Acoustic Impedance Tests↗
PubMed1988

Treatments of choice for early carcinoma of the oral cavity.

The treatment of squamous cell carcinoma of the oral cavity is determined primarily by the stage of the disease. Therapeutic modalities include surgery, radiation therapy, and chemotherapy. For patients with small, localized primary lesions and no metastases (Stages I and II), treatment might include resection of the primary tumor with or without elective neck dissection, radiotherapy to the primary tumor with or without elective neck irradiation, or combination therapy including resection of the primary tumor followed by irradiation of the neck. Patients presenting with clinically negative necks who are initially treated with elective neck dissections show better survival rates than similar patients undergoing later salvage neck dissections.

Combined Modality Therapy↗