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R Farrugia

Publications and source records attributed to R Farrugia.

13 recordsLinked to original sources

Analysing the platelet transcriptome.

Historical studies, using Northern blot hybridization, RT-PCR and cDNA library construction have demonstrated the presence of a variety of mRNA molecules in platelets. The development of microarray technology has allowed further characterization of the transcripts represented in the platelet transcriptome. In this review, these studies will be summarized and their findings in relation to the study of platelet function and the identification of disease risk genes discussed.

Blood Platelets↗

Effects of antiplatelet drugs on pulmonary responses to thrombin in anesthetized rabbits.

Platelet aggregation and fibrin deposition in the pulmonary circulation may contribute to the pathogenesis of lung injury in the adult respiratory distress syndrome (ARDS). We evaluated the effect of two antiplatelet drugs (forskolin & dipyridamole) on pulmonary responses to intravenous infusion of 100 NIH units of thrombin per kg bw in anesthetized, and ventilated rabbits treated with fibrinolysis inhibitor. Thrombin infusion resulted in pulmonary hypertension and increased arterial CO2 tension (PaCO2) and dead space ventilation (VD/VT). Arterial oxygen tension (PaO2) and numbers of circulating leukocytes and platelets dropped after thrombin infusion. These early hemodynamic changes correlated with histological evidence of entrapped leukocytes in the pulmonary microcirculation and transient alveolar edema. Microthrombi were rarely observed in animals that received thrombin. There was little evidence for endothelial damage or progressive lung water accumulation. Treatment with forskolin or dipyridamole reversed thrombin-induced changes in pulmonary artery pressure, PaCO2, VD/VT and systemic oxygenation. Moreover, forskolin and dipyridamole blunted the drop in circulating leukocytes and prevented the development of alveolar edema following thrombin. The beneficial actions of these agents may be due to interference with the release of mediators from leukocytes or platelets.

Animals↗

Interaction of thromboxane A2 and tissue pathology during graded bacteremia.

The purpose of this study was to determine whether or not thromboxane A2 (TXA2) was necessary or sufficient for the development of end-organ pathology during graded bacteremia. Pulmonary artery catheters were placed in 21 adult male pigs under pentobarbital anesthesia and breathing room air. After a control period, animals were studied in four groups: Group 1, anesthesia only; Group 2, infusion of 1 X 10(9) ml Aeromonas hydrophila which was gradually increased from 0.2 ml/kg/hr to 4.0 ml/kg/hr over 4 hours; Group 3, pretreatment with SQ 29,548 (TXA2 antagonist) then Aeromonas h. infusion; Group 4, infusion of U46619 (TXA2 agonist) to pulmonary artery pressures measured in Group 2. Animals were sacrificed after 4 hours and the lungs, liver, spleen, kidneys, and heart were examined under light microscopy by a pathologist unaware of study groups. The results indicated that physiologic thromboxane A2 agonist (Group 4) was sufficient alone to cause pulmonary inflammation. Thromboxane A2 was neither necessary nor sufficient for significant renal, hepatic, pulmonary, or splenic pathology to occur in graded bacteremia, manifested in similar microanatomic abnormalities in these organs in Groups 2 and 3 and in Groups 1 and 4. Pulmonary leukocyte infiltration was significantly increased in Group 3 compared to all other groups, suggesting that TXA2 impairs inflammatory responses.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Lung function and structure after Escherichia coli endotoxin in rabbits: effect of dose and rate of administration.

We evaluated the effect of increasing doses of Escherichia coli endotoxin and its rate of administration on systemic blood pressure, alveolar-arterial oxygen gradient (A- aDO2 1.0), dynamic compliance (Cdyn), circulating platelets and leukocytes, and postmortem bloodless wet to dry ratios in anesthetized rabbits. Infusion of endotoxin resulted in systemic hypotension, diminished Cdyn, thrombocytopenia, and leukopenia, but did not influence venous admixture. These parameters were not affected by the rapidity of administration, but changes in Cdyn and circulating platelets were dose-dependent. High (15 mg/kg), but not low (0.5 mg/kg), doses of endotoxin resulted in an early but transient increase in lung water, but bloodless wet to dry weight ratios were not increased at 4-6 h following endotoxin even when high doses were injected. Ultrastructural studies done in six rabbits showed an early but transient platelet sequestration in pulmonary capillaries, progressive increase in intracapillary leukocytes, interstitial edema, and focal, although minimal, endothelial injury at 4 h after injection. Thus, infusion of E coli endotoxin in rabbits does not result in increased lung water and intrapulmonary shunting acutely; this tolerance to endotoxin is not related to the dose or rates of administration studied.

Animals↗

Parathyroid surgery: the role of chief cell intracellular fat staining with osmium carmine in the intraoperative management of patients with primary hyperparathyroidism.

The surgeon's gross evaluation, the hematoxylin and eosin stain, which assesses extracellular fat, and a new intracellular fat stain, osmium carmine, were comparatively evaluated in 30 consecutive patients who underwent surgery for primary hyperparathyroidism. The surgeon's gross judgment of enlarged and normal parathyroid tissue resulted in the correct functional assessment in 98% and 97% of the glands, respectively. The surgeon's functional assessment was correct in seven of 10 parathyroid glands that were considered by gross examination to be slightly enlarged (50 to 80 mg). The osmium carmine intracellular fat stain provided a correct functional assessment in all 10 of these glands. The osmium carmine stain also appears to have a role in providing scientific quantitative data to limit operations in patients who have a parathyroid adenoma to removal of the adenoma and biopsy of a grossly normal gland that demonstrates normal intracellular fat. Only one side of the neck was explored in 11 patients who fulfilled these criteria. There has been no persistent or recurrent hypercalcemia in these patients.

Adenoma↗

Electrolyte versus blood cardioplegia: randomized clinical and myocardial ultrastructural study.

In 40 consecutive patients undergoing coronary artery bypass, one of two solutions for cardioplegia, each containing 30 mEq/L of K+ was used randomly. The groups were comparable except for intramyocardial temperature. With electrolyte solution (Group A), it was 16.5 degrees +/- 0.34 degrees C, while with blood from the pump-oxygenator (Group B) it was 20.3 degrees +/- 0.41 degrees C (p less than 0.001). After bypass left atrial pressure (LAP) was 11.9 +/- 0.67 torr in Group A and 8.1 +/- 0.49 torr in Group B (p less than 0.001). CPK-MB was elevated in 45% of Group A patients versus 15% in Group B (p less than 0.05). No patient died. Two myocardial infarctions occurred in Group A and one in Group B. Stereological morphometric electron microscopy was performed on biopsy specimens taken from the left ventricle (1) before perfusion, (2) after cardioplegia, and (3) 30 minutes after reperfusion. Group A showed marked intracellular edema, mitochondrial swelling, pronounced depletion of glycogen stores, and focal myofibrillary disorganization. Group B showed near normal myocardial ultrastructure with increased glycogen stores and minimal mitochondrial swelling. Morphometric analysis revealed a statistically significant increase in the degree of mitochondrial swelling (51%) in Group A compared with Group B after reperfusion (p less than 0.001). Thus, blood K+ cardioplegia resulted in better preservation of myocardial ultrastructure, lower ventricular filling pressure, and lesser CPK-MB release compared with this particular electrolyte cardioplegia.

Blood↗

Evaluation of methylene blue and squamous epithelial cells as oropharyngeal markers: a means of identifying oropharyngeal contamination during transtracheal aspiration.

The usefulness of 1% methylene blue (MB) and squamous epithelial cells as oropharyngeal markers in transtracheal aspiration was prospectively evaluated. In vitro studies showed that failure to detect MB by spectrophotometry ruled out contamination by greater than 0.05 microliters of oropharyngeal secretions and that visual inspection was almost as sensitive as spectrophotometry. Even minute contamination could be ruled out if greater than 5 x 10(4) organisms were found by culture of Gram-stained smear in a specimen that was MB-negative by spectrophotometry. In specimens of transtracheal aspirate obtained from 10 bronchitic patients, quantitative bacteriology ruled out even minute contamination in nine. Cytologic-morphometric examination revealed that 70% of both sterile and colonized specimens of transtracheal aspirate contained squamous epithelial cells that were indistinguishable, except by electron microscopy, from buccal mucosal cells. MB is a useful marker for identification of oropharyngeal contamination during transtracheal aspiration, and traditional cytologic screening is misleading in conditions associated with tracheobronchial squamous metaplasia.

Biopsy, Needle↗

Scanning electron microscopy of the surfaces of hamster embryo cells transformed by herpes simplex virus.

The surfaces of normal hamster embryo fibroblast (HEF) cells were examined by scanning electron microscopy. Surface characteristics of HEF cells were compared to those of cells derived from a primary tumor induced in hamsters following s.c. inoculation of herpes simplex virus type 1-transformed HEF cells (14-012-8-1) and to the surfaces of cells derived from a metastatic tumor to the lung induced by the same cells. The most obvious difference in the surface characteristics of the examined cells was the morphology of the microvilli. In the few HEF cells that possessed microvilli, the distribution was uneven, and the lengths of the microvilli and the filopodia were variable. However, the surfaces of both tumor cell lines showed large numbers of microvilli which were evenly distributed over the surface of the cells, giving an almost "hairy" appearance. Long filopodia were occasionally observed on the surface of the primary tumor cell line and on the cell line derived from the metastatic tumor. Ruffles and blebs were occasionally observed on HEF cells and on the primary tumor cells but were not seen on the cells of the metastatic tumor.

Animals↗