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Biomedical subjects

R Low

Publications and source records attributed to R Low.

At least 19 recordsLinked to original sources

Atypical hearing loss in women with breast cancer receiving adjuvant treatment.

There are no reports of adjuvant treatments for early breast cancer causing hearing loss. Yet in this exploratory study 14/16 women who had received Fluorouracil, Epirubicin and Cyclophosphamide (FEC) chemotherapy regimen, 11 of whom also received endocrine treatment, had reduced hearing sensitivity, with 9/16 being atypical. It is not clear whether this finding is related to oestrogen reduction and/or ototoxicity but a more detailed investigation in this area is warranted given the large number of women with breast cancer who receive adjuvant treatments.

Adult↗

Comparison of PRE-dilatation vs direct stenting in coronary treatment using the Medtronic AVE S670 Coronary Stent System (the PREDICT trial).

Current stent delivery systems make primary stenting (stent placement without predilatation) possible, but few controlled trials have been performed to evaluate the success, safety, cost saving, and potential benefit of this approach in reducing late restenosis. The Comparison of PRE-Dilatation Versus Direct Stenting In Coronary Treatment using the Medtronic AVE S670 Coronary Stent System trial was a 399-patient study comparing results with the Medtronic-AVE S670 stent to objective performance criteria based on prior approved stents, with subrandomization to direct stenting versus stenting after balloon predilatation. Overall, results with the S670 stent showed excellent success and safety, with delivery success of 99%, a 14-day adverse event rate of 6.8% (including 6.5% non-Q-wave myocardial infarction), and favorable angiographic (20%) and clinical (12%) restenosis rates. Direct stenting was successful in 92% of cases, with a 99.5% secondary success rate including additional pretreatment of initially unsuccessful direct-stenting attempts, and no increase in complications. There were modest ( approximately 10%) savings in fluoroscopy time, contrast use, and a decrease in angioplasty balloon use (0.6 vs 1.3 balloons/case), but no reduction in clinical or angiographic restenosis. Patients treated later in the study, with a device that had less balloon extension beyond the edges of the stent, had slightly lower angiographic restenosis rates (19% vs 23%). In conclusion, the S670 stent showed excellent overall performance. Although direct stenting was safe and highly successful, it offered only modest cost savings, and no reduction in late restenosis compared with stenting after predilatation.

Catheterization↗

Defining and supporting the diverse information needs of community-based care using the web and hand-held devices.

Community-based healthcare focused on maintaining wellness is becoming increasingly prevalent in the United States in an effort to eliminate healthcare disparities and reduce healthcare costs. These community-oriented initiatives, however, often require partnerships that cross traditional boundaries. As a result, these initiatives often lack a common information infrastructure to support the care delivery process. We have created and implemented a Web-based information and communication system to support the needs of a community-based healthcare project for Medicaid beneficiaries in Durham County, North Carolina. Through this project, we have identified the relevant information requirements and stakeholders for community-based care. In addition, we have explored the use of hand-held devices for accessing and collecting clinical information in the field. The overall goal of this project is to lower the costs and improve the quality of community-based healthcare through improved handling of information.

Community Health Services↗

Microvessel precursor smooth muscle cells express head-inserted smooth muscle myosin heavy chain (SM-B) isoform in hyperoxic pulmonary hypertension.

The present study analyzes smooth muscle myosin heavy chain (SMMHC) expression as lung microvascular precursor smooth muscle cells (PSMCs), cells derived from fibroblasts and intermediate cells (immature SMCs), acquire a smooth muscle phenotype in an in vivo model of pulmonary hypertension (PH). Because of the unique contractile properties of the SMMHC isoform SM-B, we analyzed its expression in the microvessels (<100 micrometers diameter) and in larger vessels (100-700 micrometers) quantitatualy by the labeled [strept]avidin-biotin technique (day 1-28), and related this to cell phenotype by transmission microscopy and protein A-gold labeling (at day 28). Airway SMCs of the normal and hypertensive lung uniformly expressed SM-B whereas vascular SMC expression was heterogeneous. Thus, in some large arteries (and veins) SMCs contained cells expressing SM-B while in others all the cells were immunonegative. Microvascular cells expressing SM-B (arteries and veins) were rare in normal lung and numerous in PH, increasing as wall muscle developed in smaller segments with time. As in large vessels, some microvessels had immunopositive cells and others only negative ones. Ultrastructural analysis confirmed that the SMCs of bronchial vessels, and the septal SMCs adjoining alveolar ducts, contained dense filament arrays decorated with SM-B. While the PSMC processes of the normal lung contained sparse filaments decorated with SM-B, these cells expressed dense filament arrays in PH. Fibroblasts migrating to align around the microvessels also expressed SM-B but in the absence of a filament network. For the first time, we demonstrate in vivo that newly developed microvascular PSMCs express the SMMHC SM-B isoform in PH.

Animals↗

Detection of reovirus RNA in hepatobiliary tissues from patients with extrahepatic biliary atresia and choledochal cysts.

Extrahepatic biliary atresia (EHBA) and choledochal cysts (CDC) are important causes of obstructive jaundice in pediatric patients. Viruses in general, and reoviruses in particular, have long been considered as possible etiologic agents responsible for inciting the inflammatory process that leads to these infantile obstructive cholangiopathies. In an effort to determine whether reovirus infection is associated with these disorders, we used a sensitive and specific reverse-transcriptase polymerase chain reaction (RT-PCR) technique designed to amplify a portion of the reovirus L1 gene segment from extracts of liver and/or biliary tissues. These tissues were obtained at the time of liver biopsy or surgical procedures from 23 patients with EHBA, 9 patients with CDC, and 33 patients with other hepatobiliary diseases. Hepatic and biliary tissues obtained at autopsy from 17 patients who died without known liver or biliary disease were also analyzed. Reovirus RNA was detected in hepatic and/or biliary tissues from 55% of patients with EHBA and 78% of patients with CDC. Reovirus RNA was found also in extracts of hepatic and/or biliary tissue from 21% of patients with other hepatobiliary diseases and in 12% of autopsy cases. The prevalence of reovirus RNA in tissues from patients with EHBA and CDC was significantly greater than that in patients with other hepatobiliary diseases (chi2 P = .012 EHBA vs. OTHER, P = .001 CDC vs. OTHER), or AUTOPSY cases (chi2 P = .006 EHBA vs. AUTOPSY, P < .001 CDC vs. AUTOPSY).

Biliary Atresia↗

Does Acanthamoeba protect Pseudomonas aeruginosa from the bactericidal effects of contact lens disinfecting systems?

PURPOSE: The aim of this study was to test the hypothesis that Pseudomonas aeruginosa that have been internalized in Acanthamoeba are protected against the action of contact lens disinfecting solutions. METHODS: The experiments were divided into two parts. First, five commercially available disinfecting solutions, hydrogen peroxide and non-peroxide based, were tested for their efficacy against four strains of P. aeruginosa and one strain of A. castellanii. Cells were inoculated into working concentrations of disinfecting solutions, incubated for 18 h and the numbers of viable bacteria or amoeba were analysed after appropriate growth on agar plates. Second, two strains of P. aeruginosa were allowed to interact with A. castellanii for 4 h prior to addition to disinfecting solutions. The numbers of P. aeruginosa after incubation with the disinfecting solutions were measured after growth on agar plates. RESULTS: In general, disinfecting solutions containing hydrogen peroxide were most effective against the micro-organisms. Solutions containing only traces of polyaminopropyl biguanide were least effective. CONCLUSIONS: For strains of P. aeruginosa, the presence of the amoebae did not protect the bacteria against the disinfecting agents. The amoeba appeared to kill the bacteria, perhaps using them as a food source.

Acanthamoeba↗

Down-regulation of plant V-type H+ -ATPase genes after light-induced inhibition of growth.

Cell extension growth in the mesocotyl tip of dark-grown Zea mays L. seedlings is dependent on vacuole enlargement and massive flux of ER and Golgi vesicles. Water flow into the expanding vacuole is driven by ion accumulation, which in turn is energized by the vacuolar H+-ATPase (V-ATPase). The V-ATPase energizes the secondary ion transport into the expanding vacuole. As light exposure leads to a strong inhibition of extension growth, the effect of light on transcript levels for subunits A and c of the V-ATPase was analyzed. Partial homologous cDNAs for subunit A and two isoforms of subunit c were cloned by RT-PCR. In dark-grown seedlings transcript levels for both subunits were much higher in the growing mesocotyl tip than in the fully differentiated mesocotyl tissue. Only in the tip region did light exposure lead to a strong and coordinate down-regulation of both mRNAs whereas in the differentiated mesocotyl only a slight decrease was observed. The results indicate that expression of the 'housekeeping' V-type H+-ATPase is strongly regulated in response to growth rate.

Adenosine Triphosphatases↗

Does a sodium-free buffer affect QRS width in experimental amitriptyline overdose?

STUDY OBJECTIVES: We carried out this study to determine the effects of pH alteration on QRS width with administration of tromethamine, a non-sodium-containing buffering agent, in experimental amitriptyline overdose. DESIGN: Prospective, nonblinded trial. PARTICIPANTS: Adult mongrel dogs. INTERVENTIONS: Pentobarbital-anesthetized dogs were overdosed with amitriptyline 5 mg/kg followed by infusion at 1.0 mg/kg/minute until the QRS width doubled, then decreased to .5 mg/kg/minute until the end of the experiment. At two defined points of toxicity, the dose of tromethamine required to raise the pH to 7.50 +/- 4 was given. pH and QRS width at a speed of 100 mm/second were measured over a 30-minute period after each tromethamine dose. Data were analyzed with non-linear-regression analysis. RESULTS: At toxicity 1 the mean pH was 7.32, with a QRS width of 11.6 mm. Two minutes after the tromethamine dose the pH rose to 7.51, with narrowing of the QRS width to 8.4 mm. At toxicity 2 the pH was 7.40, with QRS width of 10.6 mm. Two minutes after tromethamine, the pH rose to 7.49 and the QRS width decreased to 9.7 mm. Regression analysis showed a correlation between pH and QRS width; as pH increased, QRS width decreased (P = .0001). CONCLUSION: Cardiac toxicity of amitriptyline overdose, as manifested by QRS widening, is reversible by pH changes alone.

Amitriptyline↗

The 1-month outcome of patients with a low probability Technegas ventilation/perfusion lung scan.

The objective was to study the 1-month outcome of patients who had a low probability ventilation/perfusion lung scan using Technegas radioaerosol as the inhalational agent and who did not receive anticoagulation. One hundred consecutive patients with suspected pulmonary embolism were studied retrospectively. Their Technegas lung scans were classified by two blinded and independent nuclear medicine physicians and the medical records of all patients with a low probability scan were reviewed. One hundred inpatients (42 males and 58 females) with a mean age of 63 years were studied. The three most common clinical presentations leading to lung scintigraphy were unexplained dyspnoea (30 cases), unexplained dyspnoea with pleuritic chest pain (26 cases) and pleuritic chest pain only (15 cases). Nine patients had been judged by their managing medical team to have a high clinical probability of true pulmonary embolism, 32 had an intermediate probability clinical presentation and 59 a low clinical probability of pulmonary embolism. None of the 100 patients experienced further episodes of suspected or proven pulmonary embolism during the follow-up period. Six patients died. In none of them was pulmonary embolism either the cause of or a major contributing factor to death. The finding of a low probability scan using Technegas as the ventilation scintigram agent of choice describes a group of patients who, even in the absence of therapeutic anticoagulation, have a favourable 1-month outcome free of either true or suspected clinical pulmonary embolism. Invasive, pulmonary angiography-based diagnostic strategies may not be needed in this group of patients.

Female↗

Characterization of vascular smooth muscle cell phenotype in long-term culture.

Studies of bovine carotid artery smooth muscle cells, during long-term in vitro subcultivation (up to 100 population doublings), have revealed phenotypic heterogeneity among cells, as characterized by differences in proliferative behavior, cell morphology, and contractile-cytoskeletal protein profiles. In vivo, smooth muscle cells were spindle-shaped and expressed desmin and alpha-smooth muscle actin (50% of total actin) as their predominant cytoskeletal and contractile proteins. Within 24 h of culture, vimentin rather than desmin was the predominant intermediate filament protein, with little change in alpha-actin content. Upon initial subcultivation, all cells were flattened and fibroblastic in appearance with a concomitant fivefold reduction in alpha-actin content, whereas the beta and gamma nonmuscle actins predominated. In three out of four cell lines studied, fluctuations in proliferative activity were observed during the life span of the culture. These spontaneous fluctuations in proliferation were accompanied by coordinated changes in morphology and contractile-cytoskeletal protein profiles. During periods of enhanced proliferation a significant proportion of cells reverted to their original spindle-shaped morphology with a simultaneous increase in alpha-actin content (20 to 30% of total actin). These results suggest that in long-term culture smooth muscle cells undergo spontaneous modulations in cell phenotype and may serve as a useful model for studying the regulation of intracellular protein expression.

Actins↗

Alpha-smooth muscle actin in parenchymal cells of bleomycin-injured rat lung.

Bleomycin causes focally diffuse interstitial fibrosis characterized by increases in the number and volume of contractile filament-laden parenchymal cells, as well as increased parenchymal contractility. However, the origin of these cells and their relationship to altered contractility, remain unknown. We now have used immunohistochemical methods to ask if cells containing smooth muscle actin and myosin are present in involved regions of parenchyma. Staining of the parenchyma of control lungs with a monoclonal antibody against alpha-smooth muscle actin is sparse, consisting of reactivity with the alveolar entrance ring (septal tip) cells as well as occasional reactivity of alveolar wall cells that may represent pericytes or contractile interstitial cells. Increased alpha-smooth muscle actin staining was observed in areas of parenchymal damage in lungs from animals sacrificed between 1 and 4 weeks postbleomycin instillation. This reactivity included altered staining of the airway and vessel smooth muscle coat as well as thickened septal tips. In addition, newly reactive cells were observed in interstitial and intraalveolar regions and in bands of thickened submesothelial tissue. Staining was most intense in the focal fibrotic lesions which are characteristic of this injury. By contrast, parenchymal reactivity with a polyclonal antibody against smooth muscle myosin at the later time points shows only a mild increase in punctate staining in the damaged foci. We hypothesize that the substantial increase in alpha-smooth muscle actin containing cells in fibrotic regions of involved parenchyma after bleomycin injury is responsible for the altered morphologic, biochemical, and mechanical properties that we have observed.

Actins↗

Advance prediction of transthoracic impedance in human defibrillation and cardioversion: importance of impedance in determining the success of low-energy shocks.

The purposes of this study were to evaluate a method that predicts transthoracic impedance in advance of defibrillating shocks in humans and to assess the importance of transthoracic impedance in low-energy defibrillation. Via defibrillator electrodes we applied 31 kHz current to the chest during the defibrillator charge cycle, before the defibrillating shock was actually delivered. The current flow was limited by transthoracic impedance; a microprocessor monitored the predischarge current flow and determined the predischarge impedance by calibration against known resistance values. Actual impedance to the defibrillating shock was also determined and compared with the predicted impedance. With this approach we predicted impedance in 19 patients who received 66 shocks for ventricular and atrial arrhythmias. Predicted impedance (y) correlated very well with actual impedance (x):y = .90x + 11.3; r = .97. To determine the importance of impedance in defibrillation and cardioversion, we prospectively gathered data from 96 patients who received shocks of various energies for ventricular or atrial arrhythmias. In patients with high transthoracic impedance (greater than 97 omega), low-energy shocks (less than or equal to 100 J) for ventricular defibrillation had only a 20% success rate as opposed to a 70% success rate for low-energy shocks in patients with low or average impedance (p less than .05). We conclude that transthoracic impedance can be accurately predicted in advance of defibrillation and cardioversion. This method permits the preshock identification of patients with high impedance in whom attempts to defibrillate with low-energy shocks are inappropriate.

Arrhythmias, Cardiac↗

Mast cell heterogeneity and hyperplasia in bleomycin-induced pulmonary fibrosis of rats.

The distribution, density, and histochemical subtype of mast cells were studied in the respiratory tract of rats with bleomycin-induced pulmonary fibrosis. In normal rats, mast cell densities were highest in the trachea and lowest in the bronchus and parenchyma. Two histochemically distinct mast cell populations were identified in the mucosa adjacent to the tracheal cartilage, but elsewhere only a single population of typical connective tissuelike mast cells was found. After intratracheally administered bleomycin, lung histamine levels (micrograms/g wet weight) increased as much as 14-fold by Day 50. Pulmonary mast cell changes were present early in the fibrotic process, and by Day 14 the mast cell density in the parenchyma was 10 times normal. These parenchymal mast cells were histochemically of the connective tissue type. Thus, pronounced mast cell hyperplasia occurs during the evolution of experimental pulmonary fibrosis. This model provides a powerful tool to study pulmonary mast cells and to identify their role in fibrotic disease.

Animals↗