PubMed Health⌕ Search

Biomedical subjects

M Sweeney

Publications and source records attributed to M Sweeney.

At least 37 records · Page 2Linked to original sources
PubMed2000

Improved in situ detection method for telomeric tandem repeats in metaphase spreads and interphase nuclei.

Peptide nucleic acid technology (PNA) has become an extremely useful tool and promises to impact on molecular biology and diagnostics. These synthetic DNA analogues pair with DNA and RNA molecules according to Watson and Crick base pairing rules. This paper describes a sensitive and quick fluorescent in situ hybridisation (ISH) technique to determine DNA telomere repeat sequences (TTA GGG)n using epifluorescence microscopy. Telomeres are special, repeated structures at the end of each eukaryotic chromosome and serve as protective caps to prevent DNA rearrangements and fusion of chromosomes. A model system has been developed, using stimulated peripheral blood lymphocytes, which facilitates simultaneous detection of telomeres in metaphase as well as in interphase nuclei. A fluorescein isothiocyanate labelled PNA probe (18 mer) directed against complementary telomeric sequences at the end of each chromosome is used. In addition, a simple, easy to perform PNA-ISH protocol is described that overcomes common hybridisation problems encountered using DNA and RNA oligoprobes. Furthermore, the usefulness of a chromogenic immunocytochemical detection system is shown for PNA-ISH.

Humans↗
PubMed2000

Cellular localisation of HHV-8 in Castleman's disease: is there a link with lymph node vascularity?

AIMS: Human herpesvirus 8 (HHV-8) has been identified in multicentric Castleman's disease and in angioimmunoblastic lymphadenopathies. However, the presence of the virus does not necessarily indicate an aetiological role in these conditions. This study investigates the cell types infected by HHV-8 in Castleman's disease and examines the correlation between HHV-8 and Castleman's disease lymph node angiogenesis. METHODS: Sixteen formalin fixed, paraffin wax embedded samples from patients with Castleman's disease (six multicentric, 10 solitary) were examined for the presence of HHV-8 using the polymerase chain reaction (PCR), non-isotopic in situ hybridisation, PCR in situ hybridisation (PCR-ISH), and real time quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26), and viral (v)-cyclin encoding regions. Vascularity was assessed using CD34, CD31, and factor VIII immunocytochemistry, and lymph nodes were scored as "low" or "high". RESULTS: Five multicentric Castleman's disease and two solitary Castleman's disease biopsies were positive for HHV-8. HHV-8 was identified in approximately 10% of intranodal B lymphocytes, in endothelial cells, and in subcapsular spindle cell proliferations. The copy number of HHV-8 was low at 10-50 copies/1000 cells. The highest copy number was in subcapsular spindle cells. There was no correlation between vascularity score and HHV-8 status. CONCLUSION: The preferential localisation of HHV-8 in subcapsular spindle cell proliferations (where early intranodal Kaposi's sarcoma initiates) and endothelial cells in Castleman's disease might finally explain the link between intranodal Kaposi's sarcoma and Castleman's disease.

Adult↗
PubMed2000

Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling.

Chronic hypercapnia is commonly found in patients with severe hypoxic lung disease and is associated with a greater elevation of pulmonary arterial pressure than that due to hypoxia alone. We hypothesized that hypercapnia worsens hypoxic pulmonary hypertension by augmenting pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction (HPV). Rats were exposed to chronic hypoxia [inspiratory O(2) fraction (FI(O(2))) = 0.10], chronic hypercapnia (inspiratory CO(2) fraction = 0.10), hypoxia-hypercapnia (FI(O(2)) = 0.10, inspiratory CO(2) fraction = 0.10), or room air. After 1 and 3 wk of exposure, muscularization of resistance blood vessels and hypoxia-induced hematocrit elevation were significantly inhibited in hypoxia-hypercapnia compared with hypoxia alone (P < 0.001, ANOVA). Right ventricular hypertrophy was reduced in hypoxia-hypercapnia compared with hypoxia at 3 wk (P < 0.001, ANOVA). In isolated, ventilated, blood-perfused lungs, basal pulmonary arterial pressure after 1 wk of exposure to hypoxia (20.1 +/- 1.8 mmHg) was significantly (P < 0.01, ANOVA) elevated compared with control conditions (12.1 +/- 0.1 mmHg) but was not altered in hypoxia-hypercapnia (13.5 +/- 0.9 mmHg) or hypercapnia (11.8 +/- 1.3 mmHg). HPV (FI(O(2)) = 0.03) was attenuated in hypoxia, hypoxia-hypercapnia, and hypercapnia compared with control (P < 0.05, ANOVA). Addition of N(omega)-nitro-L-arginine methyl ester (10(-4) M), which augmented HPV in control, hypoxia, and hypercapnia, significantly reduced HPV in hypoxia-hypercapnia. Chronic hypoxia caused impaired endothelium-dependent relaxation in isolated pulmonary arteries, but coexistent hypercapnia partially protected against this effect. These findings suggest that coexistent hypercapnia inhibits hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy, reduces HPV, and protects against hypoxia-induced impairment of endothelial function.

Animals↗
PubMed2000

Metastatic ocular melanoma to the left ventricle inducing near-syncope attacks in an 84-year-old woman.

Cardiac tumors may represent mechanical causes for syncope by limiting left ventricular filling and/or by obstructing the left ventricular outflow tract. Malignant melanoma is known to metastasize to the myocardium or pericardium, but there are only a very limited number of reports describing endocardial involvement by the tumor. We describe herein an 84-year-old woman who presented with daily near-syncope episodes, 9 years after treatment for a choroidal melanoma. The echocardiography and the pathologic examination revealed a metastatic melanoma. This is the first reported case of an ocular melanoma metastasizing to the heart and presenting as a left ventricular intracavitary pedunculated mass.

Aged↗
PubMed1999

Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease.

Erectile dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil citrate, an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with erectile dysfunction of various etiologies. Sildenafil administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) of sildenafil in patients with erectile dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receive sildenafil (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question ("Did the treatment improve your erections?"). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with erectile dysfunction and ischemic heart disease were significantly higher for the sildenafil group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who received sildenafil and by 20% of those in the placebo group p <0.0001). For the sildenafil group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the overall incidence of cardiovascular adverse events other than flushing was comparable in patients with and without ischemic heart disease for both treatment groups. Since there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for erectile dysfunction. Physicians should be aware that patients with underlying cardiovascular disease could be adversely affected by the vasodilator effects of sildenafil, especially in combination with sexual activity. The results of the present subanalysis indicate that oral sildenafil significantly improves erectile function and is well tolerated in patients with erectile dysfunction and ischemic heart disease who are not taking nitrate therapy.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

Clinical pharmacokinetics of doxazosin in a controlled-release gastrointestinal therapeutic system (GITS) formulation.

AIMS: A controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin mesylate, a long-acting selective alpha1-adrenoceptor antagonist, was developed to enhance the pharmacokinetic profile and simplify the titration schedule by precisely controlling drug delivery rate, permitting an initial dose of 4 mg once daily, compared with standard doxazosin, which is initiated at 1 mg day-1 and titrated to a higher therapeutically effective dose. The aim of the present work was to evaluate the pharmacokinetics and bioavailability of doxazosin GITS with respect to the effect of food, age and gender, and multiple dosing. In addition, in vitro performance was assessed in conditions simulating the gastrointestinal environment. METHODS: A three-way crossover study in 24 subjects assessed the comparative bioavailability of doxazosin GITS under fed and fasting conditions and doxazosin standard under fasting condition. A multiple-dose, two-way crossover study in 35 subjects assessed the comparative pharmacokinetics and bioavailability of doxazosin GITS and doxazosin standard 4 and 8 mg upon multiple dosing. A multiple-dose, four-parallel-group study was conducted to determine the steady-state pharmacokinetics and bioavailability of doxazosin GITS 4 mg in 41 young and elderly male and female subjects. The release-rate profiles of doxazosin GITS were determined in artificial gastric fluid (pH=1.2), intestinal fluid (pH=7.5), and water. The effect of agitation on the dissolution characteristics of doxazosin GITS in artificial gastric fluid was studied at stirring rates of 50, 75, and 100 rev min-1. RESULTS: In vitro studies demonstrated that release rates for the GITS tablet are independent of pH in the range of 1.2 (gastric) to 7. 5 (intestinal), and of stirring rates simulating gastrointestinal motility. Clinical pharmacology studies showed that doxazosin GITS had a lower maximum plasma concentration, prolonged time to reach maximum plasma concentration, and a higher minimum plasma concentration compared with doxazosin standard. Thus, the GITS formulation results in a more gradual absorption of doxazosin, and a reduced plasma doxazosin concentration peak-to-trough fluctuation ratio. The relative bioavailability of doxazosin GITS is approximately 60%. With a high-fat meal, the maximum plasma concentration and area under the concentration-time curve were 31% and 18% higher, respectively (P<0.05). Bioequivalence was established between the dose strengths of two 4 mg doxazosin GITS tablets and one 8 mg doxazosin GITS tablet. For both young adult and elderly subjects, and males and females, the pharmacokinetics of doxazosin GITS once daily for 7 days were comparable. Doxazosin GITS was well tolerated in the subjects studied, including young and elderly males and females. CONCLUSIONS: The GITS formulation of doxazosin enhances the pharmacokinetic profile compared with doxazosin standard, allowing more gradual absorption of doxazosin, and a reduced plasma doxazosin peak-to-trough concentration ratio. Thus, doxazosin GITS therapy can be initiated at a therapeutic dose of 4 mg with reduced haemodynamic side-effects.

Adult↗
PubMed1999

Effects of changes in pH and PCO2 on wall tension in isolated rat intrapulmonary arteries.

We examined mean ( S.E.M.) changes in wall tension in isolated rat intrapulmonary arteries on switching from control conditions (pH 7.38 +/- 0.01; PCO2, 34.4 +/- 0.5 mmHg) to hypercapnic acidosis (pH change, -0.24 +/- 0.01; PCO2 change, +27.5 +/- 0.9 mmHg), isohydric hypercapnia (pH change, -0.02 +/- 0.01; PCO2 change, +28.5 +/- 0.8 mmHg) and normocapnic acidosis (pH change, -0.24 +/- 0.01; PCO2 change, -0.5 +/- 0.3). Arteries were submaximally preconstricted with prostaglandin F2 and changes in tension are expressed as a percentage of the 80 mM KCl-induced contraction (%Po). Mean changes in wall tension on switching to hypercapnic acidosis (+4.4 +/- 3.7 %Po), isohydric hypercapnia (+1.9 +/- 2.2 %Po) and normocapnic acidosis (-1.5 +/- 1.9 %Po) were not significantly different from the change observed on switching to control conditions (+3.5 +/- 1.1 %Po), and were unaltered by endothelial removal. In isolated carotid preparations, the change in tension in isohydric hypercapnia (-6.8 +/- 7.1 %Po) was not significantly different from that observed in control switches (+8.6 +/- 3.2 %Po). Significant reductions in tension (P < 0.001) were observed in hypercapnic (-42.9 +/- 7.8 %Po) and normocapnic acidosis (-36.4 +/- 9.0 %Po). These data suggest that intrapulmonary arteries are resistant to the vasodilator effects of extracellular acidosis observed in systemic (carotid) vessels.

Acidosis↗
PubMed1998

Identification of a retinoic acid responsive aldoketoreductase expressed in HL60 leukaemic cells.

Neutrophil and monocyte differentiation can be induced in HL60 leukaemia cells by all-trans-retinoic acid (ATRA) and 1alpha,25-dihydroxyvitamin D3 (D3), respectively, whose differentiating effects can be enhanced by exposure to 'anti-inflammatory agents' and steroids. We have provided evidence that this potentiation is via inhibition of the activity of an enzyme of the aldoketoreductase (AKR) family, but had failed to identify expression of known AKRs in HL60 cells. In this study, we have identified a previously unclassified aldoketoreductase family member (termed HAKR e) that is expressed in HL60 cells. HAKR e is dramatically and transiently up-regulated in HL60 cells within 24 h of exposure to ATRA, further supporting the proposition that a member(s) of this family of enzymes play(s) a role in controlling cell growth and/or differentiation.

Blotting, Northern↗
PubMed1998

Differences in Chlorophyll Loss at 13 degrees C for Two Broccoli (Brassica oleracea L.) Cultivars Associated with Antioxidant Enzyme Activities.

Two broccoli cultivars which have been previously found to have large differences in yellowing susceptibility were studied to determine if there was a relationship between antioxidant capability and chlorophyll loss at a simulated retail display temperature. Greenbelt cultivar retained a stable chlorophyll content over 4 days at 13 degrees C, while Emperor cultivar showed a constant decline in chlorophyll content. These differences were not related to differences in water loss. Superoxide dismutase (SOD) and peroxidase (POD) activities were approximately 30% higher in Greenbelt than in Emperor. The ratio of superoxide dismutase to peroxidase activity was also lower in Greenbelt. The susceptibility of Emperor to oxygen radical damage and lipid peroxidation is expected to be higher since an excessive SOD activity, with respect to POD activity, can potentially lead to enhanced hydroxyl radical formation. Catalase (CAT) activity was higher in Emperor, suggesting that catalase is not important in providing resistance to chlorophyll loss in broccoli. Water soluble, nonenzymatic antioxidant activity was similar for both cultivars. These results support the hypothesis that antioxidant protection offered by superoxide dismutase and peroxidase is important to retention of green color in broccoli.

Journal Article↗
PubMed1998

Effects of changes in pH and CO2 on pulmonary arterial wall tension are not endothelium dependent.

We examined the changes in isolated pulmonary artery (PA) wall tension on switching from control conditions (pH 7.38 +/- 0.01, PCO2 32.9 +/- 0.4 Torr) to isohydric hypercapnia (pH change 0.00 +/- 0.01, PCO2 change 24.9 +/- 1.1 Torr) or normocapnic acidosis (pH change -0.28 +/- 0.01, PCO2 change -0.3 +/- 0.04 Torr) and the role of the endothelium in these responses. In rat PA, submaximally contracted with phenylephrine, isohydric hypercapnia did not cause a significant change in mean (+/- SE) tension [3.0 +/- 1.8% maximal phenylephrine-induced tension (Po)]. Endothelial removal did not alter this response. In aortic preparations, isohydric hypercapnia caused significant (P < 0.01) relaxation (-27.4 +/- 3.2% Po), which was largely endothelium dependent. Normocapnic acidosis caused relaxation of PA (-20.2 +/- 2.6% Po), which was less (P < 0.01) than that observed in aortic preparations (-35.7 +/- 3.4% Po). Endothelial removal left the pulmonary response unchanged while increasing (P < 0.01) the aortic relaxation (-53.1 +/- 4.4% Po). These data show that isohydric hypercapnia does not alter PA tone. Reduction of PA tone in normocapnic acidosis is endothelium independent and substantially less than that of systemic vessels.

Acetylcholine↗
PubMed1998

Identifying psychological contributions to chronic pain complaints with the MMPI-2: the role of the K scale.

Although the 1-3/3-1 Minnesota Multiphasic Personality Inventory (MMPI) code type is traditionally interpreted as suggesting that somatic complaints are caused or exacerbated by psychological factors, prior research has raised questions about the validity of this interpretation for chronic pain patients. This study examined alternative strategies for using the MMPI to identify psychological contributions to chronic pain complaints. A sample of 125 chronic pain patients completed the MMPI-2. They were also rated by clinical staff on a set of descriptive statements reflecting psychological features that can contribute to physical complaints. MMPI patterns that are traditionally used to identify these features, such as the 1-3/3-1 code type, were not related to the ratings. A relation was found between scores on the K scale and the ratings, where patients with higher scores on the K scale (T > or = 56) received ratings suggesting less of a psychological contribution to their pain complaints. The implications of the findings for understanding the nature of the K scale are discussed.

Adaptation, Psychological↗
PubMed1998

Linked pacing after heterotopic heart transplantation with concurrent left ventricular reduction of the native heart.

A 30-year-old man with dilated cardiomyopathy underwent heterotopic heart transplantation, concurrently with surgical reduction of the native left ventricle, a mitral valvuloplasty, and an apical thrombectomy. Postoperatively, the patient had hemodynamic instability that was refractory to conventional medical therapy. Temporary sequential pacing of the 2 hearts was used to induce timed counterpulsation, which resulted in marked hemodynamic improvement. To the best of our knowledge, this case involves the 1st report in the English-language literature of clinical usage of paced, linked counter-pulsation to treat acute hemodynamic compromise early after heterotopic heart transplantation.

Adult↗
PubMed1997

Neocentromere-mediated chromosome movement in maize.

Neocentromere activity is a classic example of nonkinetochore chromosome movement. In maize, neocentromeres are induced by a gene or genes on Abnormal chromosome 10 (Ab10) which causes heterochromatic knobs to move poleward at meiotic anaphase. Here we describe experiments that test how neocentromere activity affects the function of linked centromere/kinetochores (kinetochores) and whether neocentromeres and kinetochores are mobilized on the spindle by the same mechanism. Using a newly developed system for observing meiotic chromosome congression and segregation in living maize cells, we show that neocentromeres are active from prometaphase through anaphase. During mid-anaphase, normal chromosomes move on the spindle at an average rate of 0.79 micron/min. The presence of Ab10 does not affect the rate of normal chromosome movement but propels neocentromeres poleward at rates as high as 1.4 micron/min. Kinetochore-mediated chromosome movement is only marginally affected by the activity of a linked neocentromere. Combined in situ hybridization/immunocytochemistry is used to demonstrate that unlike kinetochores, neocentromeres associate laterally with microtubules and that neocentromere movement is correlated with knob size. These data suggest that microtubule depolymerization is not required for neocentromere motility. We argue that neocentromeres are mobilized on microtubules by the activity of minus end-directed motor proteins that interact either directly or indirectly with knob DNA sequences.

Anaphase↗
PubMed1997

In vivo skeletal muscle mitochondrial function in Leber's hereditary optic neuropathy assessed by 31P magnetic resonance spectroscopy.

We used 31P magnetic resonance spectroscopy (31P-MRS) to assess in vivo skeletal muscle mitochondrial function in 10 Leber's hereditary optic neuropathy patients/carriers with a mitochondrial DNA (mtDNA) mutation at one of three nucleotide positions, 11,778, 14,484, and 3,460. We studied one affected patient for each mutation and two unaffected carriers with the 11,778 or 3,460 mutation and three carriers with 14,484. All subjects were homoplasmic except the two 3,460 carriers, who showed 80% and 15% of mutated mtDNA. 31P-MRS at rest disclosed some abnormalities in all subjects. In particular, the phosphorylation potential was below the normal range in all cases. During recovery from exercise, the maximum rate of mitochondrial ATP production (Vmax) was reduced to 27% of normal in the 11,778 mutation and to 53% in the 14,484 mutation patient/carrier groups. Mitochondrial Vmax was within the normal range in all subjects with the 3,460 mutation but correlated inversely with the percentage of mutated mtDNA. This in vivo study shows that the 11,778 mutation causes a mitochondrial impairment more severe than the 14,484 and that the 3,460 mutation results in only a mild depression of muscle mitochondrial function.

Adult↗
PubMed1997

Constipation. Diagnosis and treatment.

Chronic constipation, the number one gastrointestinal complaint in the United States, is a serious condition that affects patient quality of life and accounts for the annual expenditure of millions of dollars by affected individuals, many of whom attempt to self-manage their condition. Because constipation has varied etiologies and treatment modes, it is imperative for the family nurse practitioner to know options for patients. Constipation complaints can indicate multiple diseases, and such patients can be among the most difficult diagnostic and therapeutic problems in clinical practice. Two of the primary care provider's duties to these patients are to educate them about bowel habits and to explain how different medications may either aid or exacerbate their symptoms. Constipation is a universal affliction of Western civilization. In the United States, this malady accounts for more than 2.5 million physician visits per year, is among the most frequent reasons for self-medication, and is particularly troublesome in the elderly population. Americans spend more than $725 million annually on over-the-counter (OTC) laxatives in an attempt to self-treat the most common gastrointestinal complaint in the country.

Cathartics↗