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Biomedical subjects

M Kearney

Publications and source records attributed to M Kearney.

At least 91 records · Page 5Linked to original sources
PubMed1994

Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women.

BACKGROUND: The relative absence of coronary atherosclerosis in premenopausal women has been established. Estrogen is presumed to play a role in the protection of coronary arteries from atherosclerosis, and part of this protective effect appears to be mediated by amelioration of serum lipid profiles. However, all of the atheroprotective effect of estrogen is not explained by alteration of serum lipids. In this study, we attempt to identify evidence of estrogen receptors in coronary artery specimens of female patients and in human vascular smooth muscle cells. METHODS AND RESULTS: Postmortem coronary artery specimens were obtained from premenopausal (n = 18) and postmenopausal (n = 22) women who died with significant coronary artery disease (n = 19) and from noncardiac causes with normal coronary arteries (n = 21). Sections were examined for evidence of estrogen receptor expression using a monoclonal antibody stain. Radioligand binding assays for estrogen receptors were performed on human vascular smooth muscle cells in culture, and gel retardation assays were performed to confirm the presence of functional estrogen receptors. Estrogen receptor expression was identified by immunostaining in a total of 21 coronary arteries, with the majority of normal arteries (15 positive of 21 total, P = .0117) demonstrating evidence of estrogen receptor expression. Conversely, a minority (6 of 19, P = NS) of atherosclerotic arteries were positive for estrogen receptor expression. Furthermore, the relation between estrogen receptor expression and absence of coronary atherosclerosis was most evident in premenopausal subjects, with 10 of 12 normal arteries in this group demonstrating evidence of estrogen receptors, whereas only 1 of 6 atherosclerotic coronary arteries was positive (P = .0062). Radioligand binding assays confirmed the presence of estrogen receptors at significant concentrations in intact human vascular smooth muscle cells. Gel retardation assays also documented the presence of functional estrogen receptors in extracts from human vascular smooth muscle cells. CONCLUSIONS: This investigation provides evidence of estrogen receptors in smooth muscle cells from human coronary arteries. The demonstrated relation between the presence of the receptors and the absence of atherosclerosis in premenopausal women suggests that these receptors may play a functional role in coronary atheroprotection.

Adult↗
PubMed1994

Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.

Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF was administered as a single intra-arterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,000 micrograms of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.75 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.

Angiography↗
PubMed1994

Time course of recombinant protein secretion after liposome-mediated gene transfer in a rabbit arterial organ culture model.

BACKGROUND: Little information exists regarding the time course of gene expression after arterial transfection. Accordingly, we sought to determine the time course of gene expression after liposome-mediated arterial gene transfer (lipofectin) using an arterial organ culture model. EXPERIMENTAL DESIGN: Explanted segments of rabbit descending thoracic aorta were maintained in organ culture. Arterial gene transfer, facilitated by cationic liposomes (Lipofectin), was performed with the plasmid pXGH5 encoding the human growth hormone (hGH) under the control of mouse metallothionein-1 promoter. RESULTS: The time course of hGH production after transfection with the plasmid pXGH5 was evaluated. Significant levels (181.0 +/- 33.9 ng/24 hours/gm) of hGH were detected within 24 hours post-transfection, reached a peak on day 7 (238.4 +/- 35.3 ng/24 hours/gm), and declined after day 10. At day 21, hGH could be observed in 50% of the arteries. Immunostaining with a monoclonal antibody for hGH revealed that only a small number of arterial cells (< 1%) were responsible for production of hGH. CONCLUSIONS: The organ culture model is a feasible and efficient means for investigating the kinetics of arterial gene transfer. Transfection of pXGH5 results in significant levels of hGH for up to 3 weeks, despite anatomic evidence of only limited gene expression. These data thus support the notion that the magnitude and/or duration of gene expression may be disproportionately high, relative to anatomic assessment of transfection efficiency in the case of a transgene encoding for a secreted protein.

Animals↗
PubMed1993

[Pleuropulmonary actinomycosis].

A previously healthy 42 years old male was admitted to hospital with chest pain. Chest radiograms revealed a solid mass in the left thoracic cavity. A lung biopsy showed findings consistent with probable actinomycosis. It was feared that the specimen was not representative and a left upper lobe lobectomy was performed. This confirmed the diagnosis of actinomycosis. The patient was postoperatively treated with penicillin and tetracycline and has remained well during a follow-up period of two years.

Actinomycosis↗
PubMed1993

Suitable screening tests for cognitive impairment and depression in the terminally ill--a prospective prevalence study.

Although confusional states and depression are common accompaniments of advanced cancer, few objective data are available concerning the prevalence of these clinical states or what methods are most suitable for their accurate detection. We decided that a 10-question Abbreviated Mental Test Score (AMTS) and a semistructured application of modified DSMIII-R (Diagnostic and Statistical Manual of Mental Disorder, third edition-revised) criteria for a major depressive illness were the most suitable screening tests for a terminally ill population. Thirty of 87 patients (34%) displayed significant cognitive impairment. The AMTS rating declined with approaching death and also correlated negatively with age. Of 81 patients, 21 (26%) were depressed when screened using DSMIII-R criteria for depression. One-third of patients with impaired AMTS scores also satisfied DSMIII-R criteria for depression. Of cognitively impaired patients, 90% had at least two possible causes for their confused state. We have found that both the AMTS and semistructured interview using DSMIII-R criteria for depression are useful routine screening tests in the terminally ill.

Adult↗
PubMed1992

Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy.

BACKGROUND: Identification of genes that are specifically activated in restenosis lesions after percutaneous transluminal angioplasty represents a necessary step toward molecular manipulation designed to inhibit cellular proliferation responsible for such lesions. Whereas quiescent smooth muscle cells (contractile phenotype) preferentially express smooth muscle myosin, proliferating smooth muscle cells (synthetic phenotype) have been shown to preferentially express nonmuscle myosin in vitro. Accordingly, we analyzed the expression of a recently cloned isoform of human nonmuscle myosin heavy chain (MHC-B) in fresh human restenotic lesions. METHODS AND RESULTS: A total of 10 lesions, including four restenosis (three superficial femoral arterial lesions and one saphenous vein bypass lesion) and six primary (four superficial femoral arterial lesions and two coronary arterial lesions) obtained percutaneously by directional atherectomy, were processed for examination by in situ hybridization. In total, 150 tissue sections of restenotic lesions (66 sections), primary lesions (78 sections), and normal internal mammary artery (six sections) were hybridized with the nonmuscle MHC-B probe. Restenotic lesions showed intense hybridization to the nonmuscle MHC-B cRNA probe, as demonstrated by a clustering of more than 20 grains per cell nucleus in 80% of the cells examined within a high-power field (x250); in contrast, an equivalent degree of hybridization was observed in only 7% of cells within primary lesions (p less than 0.001). Results of immunocytochemistry using monoclonal antibody to smooth muscle actin indicated that cells demonstrating strong hybridization were smooth muscle in origin. CONCLUSIONS: These findings demonstrate that 1) human vascular tissue obtained by percutaneous directional atherectomy constitutes appropriate biopsy material for gene expression studies at the mRNA level, and 2) nonmuscle MHC-B mRNA is present in greater abundance among restenotic versus primary vascular stenoses. These observations thus provide a rational basis to explore restenotic lesions on a larger scale to identify genes that are activated in these lesions and establish potential targets for future gene therapy.

Arteriosclerosis↗
PubMed1992

In vivo assessment of vascular pathology resulting from laser irradiation. Analysis of 23 patients studied by directional atherectomy immediately after laser angioplasty.

BACKGROUND: The pathological consequences of cardiovascular laser irradiation have been studied extensively in vitro. Previous in vivo studies of laser-induced injury have included analyses of acute and/or chronic findings in experimental animals. Little information, however, is available regarding the acute effects of laser irradiation of human vascular tissues in vivo. METHODS AND RESULTS: To determine the acute pathology resulting from laser irradiation of human vascular tissue in vivo, specimens retrieved from 23 patients by directional atherectomy immediately after laser angioplasty (19 peripheral and four coronary) were examined by light microscopy. Of the 23 patients, three (13.0%) were treated with a metal-capped ("hot-tip") fiber coupled to a continuous-wave neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using up to 18 W power and 18-305 seconds of cumulative exposure time; in all three patients (100%), thermal injury, including frank charring several cell layers thick, was seen along the luminal borders of the atherectomy specimen. In eight of the 23 patients (34.5%), laser angioplasty was performed using a 250-microseconds holmium:YAG laser at fluences up to 2,300 mJ/mm2, a repetition rate of 5 Hz, and 25-200 seconds of cumulative exposure; in seven of eight patients (85.5%), the atherectomy specimen showed signs of vacuolar injury consisting of central and satellite Alcian-blue-negative vacuoles. In two patients (25.0%), there was a "smudged" or "shredded" edge, whereas in one patient, frank signs of thermal injury were observed. Finally, in 12 of the 23 patients (52.2%), laser angioplasty was performed using a 120-nsec excimer laser at fluences up to 60 mJ/mm2, a repetition rate of 25 Hz, and a cumulative exposure time of 21-315 seconds. Pathological findings among these 12 patients were limited to nine patients (75%) in whom a weakly basophilic, smudged, and/or shredded appearance approximately one cell layer thick was observed along the luminal border of the atherectomy specimen and two patients (16.7%) with small foci of vacuolar injury. None of the atherectomy specimens retrieved after excimer laser angioplasty disclosed signs of thermal injury. CONCLUSIONS: These findings document that acute pathological alterations resulting from in vivo laser angioplasty are variable, depending on the laser source used, and are similar to that predicted by experimental studies performed previously in vitro. The prognostic implications of these varying pathological features remain to be clarified.

Aged↗
PubMed1992

Expression of transforming growth factor-beta 1 is increased in human vascular restenosis lesions.

Human atheromata obtained in vivo were used to test the hypothesis that transforming growth factor-beta 1 plays a role in the development of vascular restenosis. We analyzed 28 specimens from patients with primary atherosclerotic or restenotic lesions; 26 of these were obtained by directional atherectomy and 2 at the time of coronary bypass surgery. Seven control tissues included operatively excised segments of human internal mammary artery, myocardium, and unused portions of vein graft obtained intraoperatively. From these 35 specimens, 210 sections were examined using in situ hybridization. Measurement of silver grains/nucleus disclosed that expression of transforming growth factor-beta 1 mRNA was highest in restenotic tissues (P < 0.001 vs. primary atherosclerotic tissues) and lowest in nonatherosclerotic (control) tissues. In cultures of human vascular smooth muscle cells grown from explants of internal mammary artery, expression of mRNA for transforming growth factor-beta 1 was significantly greater in subconfluent than in confluent smooth muscle cells (P = 0.05). Transforming growth factor type-beta III receptor was expressed in cell cultures and undetectable in the tissue specimens. Sections taken adjacent to those studied by in situ hybridization were examined by immunohistochemistry using antibodies against transforming growth factor-beta 1 and alpha-actin (as a marker for smooth muscle cells) and disclosed transforming growth factor-beta 1 in smooth muscle cells present in these sections. These findings are consistent with the concept that transforming growth factor-beta 1 plays an important role in modulating repair of vascular injury, including restenosis, after balloon angioplasty.

Actins↗
PubMed1992

Management of the final 24 hours.

The management of the final 24 hours of life of 100 patients, dying in Our Lady's Hospice is reviewed. This review suggests that management might be improved by better contact between general hospitals and hospice/home care teams concerning the timing of patient transfer. The frequency of symptoms in the dying patient, even where many are semi-comatose, is highlighted. The main distressing symptoms are pain, excessive respiratory secretions and agitation. Our review confirms reliance on standard palliative medications such as morphine, however identifies the benefit of such newer preparations as hydromorphone and midazolam. Management might be improved by the earlier usage of hyoscine subcutaneously and stopping the use of intramuscular diazepam. Attention to potential hyoscine toxicity and untreated pyrexia may ease pre-terminal agitation. The dying patient's family also needs attention to complete the optimal management of the final 24 hours.

Adult↗
PubMed1992

Single daily bottle use in the early weeks postpartum and breast-feeding outcomes.

A prospective study of breast-feeding mothers was undertaken to determine the effects of limited bottle use and infant temperament on breast-feeding outcomes. White, married, primigravida women who were committed prenatally to breast-feeding for at least 6 weeks (n = 121) were randomly assigned to one of two groups: a planned bottle group that would offer one bottle daily between the second and sixth weeks postpartum and a total breast-feeding group that would avoid bottles during the same period. Group assignment had no effect on the occurrence of breast-feeding problems, on mothers' achievement of 90% of their prenatal breast-feeding duration goals, or on weeks to weaning across the study period. At 6 months postpartum, 59% of the planned bottle group and 69% of the total breast-feeding group were still breast-feeding. No main or interactive effects of infant temperament on breast-feeding outcomes were found.

Adult↗
PubMed1991

National survey of clinical and subclinical mastitis in Jamaican dairy herds, 1985-1986.

Between April 1985 and August 1986, 89 Jamaican dairy herds with 10 or more cows were visited, 1,645 lactating cows were examined using the CMT test and 254 composite milk samples collected for bacteriological examination. Widespread management faults were noted, especially of milking machine usage and maintenance and the abuse of antibiotics. Fifty-six per cent of all quarters were found to have CMT scores of one or higher, 0.8% showed clinical mastitis and 3.2% were blind. The most common bacterial pathogen Staphylococcus aureus, was recovered from 31% of sampled cows. The resultant milk loss from clinical and subclinical mastitis was estimated to be 20% of the potential national production.

Animals↗
PubMed1991

Remote frozen section service: a telepathology project in northern Norway.

We discuss the organization of a remote frozen section service in northern Norway. The service is operated by remote control of a motorized video-microscope located at Kirkenes Hospital, at a distance of more than 400 km from the workstation at the University Hospital in Tromsø. The video images of the frozen section are transmitted via a two-way telephone and video telenetwork with a 2 Mbit/s capacity. The images are displayed on monitors and diagnosed by pathologists in Tromsø. To date, 17 patients have been examined by remote frozen section. Correct benign versus malignant diagnoses have been given in all 17 cases compared with final diagnoses based on formalin-fixed and paraffin-embedded material. The average time taken for examining each frozen section was 15 minutes (range, 5 to 30 minutes). In none of the cases was the interpretation of the slides difficult due to deficient quality of the video images. For small hospitals with limited availability of local pathology services and for hospitals with a deficiency of specialists, telepathology may be a worthwhile substitute.

Equipment and Supplies, Hospital↗
PubMed1989

Evaluation of a mass measles immunisation campaign in a rapidly growing peri-urban area.

A mass measles immunisation campaign, with a target coverage rate of 85-90%, was launched in Khayelitsha, a rapidly growing urban township in the Cape Town area. Cross-sectional surveys of the measles immunisation status of resident 6-23-month-old infants were conducted immediately before, immediately after, and approximately 2 months after the campaign in order to determine the effectiveness of a mass campaign in boosting coverage in an area with a high influx rate. Immunisation coverage rates were 55% in the first survey, 76% in the second, and 72% in the third. In the first survey, coverage rates for children born in Cape Town were 1.4 times higher than those born elsewhere. This trend continued throughout the survey. Duration of stay in Cape Town also influenced coverage, with rates for the recently arrived children being considerably lower than those for the more established Cape Town residents. The influx rate between the second and third survey (over the Christmas period) was 9.1% per month. Failure to reach the targeted rate is attributed to the influx rate, campaign design and implementation, and factors related to child and career mobility. Alternative immunisation strategies, with social awareness playing a key role, are being urgently investigated.

Cross-Sectional Studies↗
PubMed1989

Mechanism of death in avalanche victims.

The autopsies of 12 victims from two snow avalanches in North-Norway are reported. Supportive evidence from non-autopsied and surviving victims is included. Consistent autopsy findings were prominent lung oedema, moderate cerebral oedema, extreme contraction of the left ventricle, petechiae in the superior vena cava drainage area, and acute congestion in lungs and kidneys. In four cases in whom no resuscitation was attempted, aortic oxygen pressure was in the range expected in pure asphyxial-type deaths in one and in pure cardiac-type deaths in three. No air pocket was seen in front of the mouth and nose in any of the fatal cases. Three fatal cases had fractures. It is concluded that the immediate cause of death in most cases was general body compression with acute respiratory and circulatory failure.

Adolescent↗