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Biomedical subjects

P White

Publications and source records attributed to P White.

At least 73 records · Page 4Linked to original sources
PubMed2000

Coincident microvillar actin bundle disruption and perinuclear actin sequestration in anoxic proximal tubule.

The present studies investigated acute disruption of microvillar actin cytoskeleton and actin association with other cytoskeletal components in ATP-depleted rabbit proximal tubular cells. Video-enhanced differential-interference contrast microscopy and confocal microscopy were used to follow the fate of F-actin during the disruption of microvilli. Within individual cells, all microvilli collapsed simultaneously. Microvillar actin filaments underwent a parallel decrease in length. Using a sequential cytoskeletal extraction protocol and electron microscopy, we revealed in the present studies the coincident sequestration of a distinct, perinuclear pool of actin that was primarily absent in control cells. Actin sequestration progressed in a duration-dependent manner, occurring as early as 15 min of anoxia when cellular ATP dropped to <5% of control level. Phalloidin staining and depolymerization treatment showed the majority (>90%) of this sequestered actin to be F-actin. A microvillar actin bundling protein villin was also sequestered in the same perinuclear complex of anoxic proximal tubules. In conclusion, the present results demonstrate a coincident microvillar actin bundle disruption and the perinuclear sequestration of F-actin in ATP-depleted proximal tubular cells.

Actins↗
PubMed2000

Predictors of pain control in patients undergoing flexible bronchoscopy.

The purpose of this study was to assess the extent to which patients undergoing flexible bronchoscopy (FOB) experience pain and to identify patient factors and process of care factors that are associated with pain. We conducted a prospective cohort study on 481 patients undergoing FOB. Overall control of pain during FOB was the primary outcome. The mean age of the patients was 48 yr, 50% were male, and 32% required supplemental oxygen prior to FOB. Pain control was excellent in 36% of patients, but 10% considered it to be fair or poor. Patient factors associated with excellent pain control were excellent health (versus poor health, OR = 6.25 [95% CI, 2.28-16.67]), more education (college education versus high school education, OR = 1.72 [95% CI, 1.05-2.86]), and not having asthma (OR = 2.86 [95% CI, 1.09-7.14]). Process of care factors associated with excellent pain control were not being bothered by scope insertion (versus bothered, OR = 3.65 [95% CI, 1.99-6.98]), no memory of FOB (versus some memory, OR = 2.33 [95% CI, 1.24-4.44]), and higher ratings of information about the procedure (per 1-point increase on a 12-point scale, OR = 1.57 [95% CI, 1.41-1.78]). This is the first large-scale, prospective study to evaluate patient and process of care factors that influence pain control during FOB. It demonstrated that there are patient characteristics and process of care factors that need to be considered when evaluating pain during bronchoscopy. Improved preparation of patients with lower education, inferior health status, and asthma may lead to decreased pain during FOB. Bronchoscopists may be able to reduce pain during FOB by identifying methods to decrease pain on scope insertion, by improving the information provided to patients, and by achieving greater levels of amnesia during FOB.

Adolescent↗
PubMed2000

Utility of on-site cytopathology assessment for bronchoscopic evaluation of lung masses and adenopathy.

STUDY OBJECTIVES: To determine the extent to which on-site cytopathology assessment improves diagnostic yield when sampling lung nodules or masses and/or hilar or mediastinal lymphadenopathy by fiberoptic bronchoscopy (FOB). DESIGN: Prospective cohort study. SETTING: Two teaching hospitals in Baltimore, MD. PATIENTS: Consecutive adult patients (>/= 18 years) undergoing FOB for evaluation of lung nodules or masses and/or hilar or mediastinal lymphadenopathy. INTERVENTION: Prospective collection of data on patient factors and details of the procedure on standardized report forms. MEASUREMENTS AND RESULTS: The primary outcome measure was a new diagnosis obtained by FOB. On-site assessment was used in 81 of 204 cases (40%), and overall diagnostic yield was 62%. Yield was greater when on-site cytopathology assessment was used, in unadjusted analysis (81% vs 50%, p < 0.001) and in a multivariate model (odds ratio, 4.5; 95% confidence interval, 2.1 to 10.0). Other significant predictors of a new diagnosis included older patient age, higher dose of narcotic used during FOB, and shorter procedure time. CONCLUSIONS: We conclude that diagnostic yield was greater when on-site cytopathology was used to assist FOB evaluation of intrathoracic adenopathy and/or lung nodules or masses. Increasing the use of on-site cytopathology assessment may improve the quality of FOB services.

Adolescent↗
PubMed2000

Three-dimensional CT-guided bronchoscopy with a real-time electromagnetic position sensor: a comparison of two image registration methods.

STUDY OBJECTIVES: To compare two different image registration methods for accurately displaying the position of a flexible bronchoscope on a previously acquired three-dimensional CT scan during bronchoscopy. SETTING: Bronchoscopy suite of a university hospital. PATIENTS: Fifteen adult patients scheduled for nonemergent bronchoscopy. METHODS: A miniature electromagnetic position sensor was placed at the tip of a flexible bronchoscope. Previously acquired three-dimensional CT scans were registered with the patient in the bronchoscopy suite. Registration method 1 used multiple skin fiducial markers. Registration method 2 used the inner surface of the trachea itself for registration. Method 1 was objectively assessed by measuring the error distance between the real skin marker position and the computer display position. Methods 1 and 2 were subjectively assessed by the bronchoscopist correlating visual bronchoscopic anatomic location with the computer display position on the CT image. RESULTS: The error distance (+/- SD) from known points for registration method 1 was 5.6 +/- 2.7 mm. Objective error distances were not measured for method 2 because no accurate placement of the bronchoscope sensor could be correlated with CT position. Subjectively, method 2 was judged more accurate than method 1 when compared with the fiberoptic view of the airways through the bronchoscope. Additionally, method 2 had the advantage of not requiring placement of fiducial markers before the CT scan. Respiratory motion contributed an error of 3.6 +/- 2.6 mm, which was partially compensated for by a second tracking sensor placed on the patient's chest. CONCLUSION: Image registration method 2 of surface fitting the trachea rather than method 1 of fiducial markers was subjectively judged to be superior for registering the position of a flexible bronchoscope during bronchoscopy. Method 2 was also more practical inasmuch as no special CT scanning technique was required before bronchoscopy.

Biopsy↗
PubMed2000

Postnatal regulation of myosin heavy chain isoform expression and metabolic enzyme activity by nutrition.

Development of muscle is critically dependent on several hormones which in turn are regulated by nutritional status. We therefore determined the impact of mild postnatal undernutrition on key markers of myofibre function: type I slow myosin heavy chain (MyHC) isoform, myosin ATPase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase. In situ hybridization, immunocytochemistry and enzyme histochemistry were used to assess functionally distinct muscles from 6-week-old pigs which had been fed an optimal (6% (60 g food/kg body weight per d)) or low (2% (20 g food/kg per d)) intake for 3 weeks, and kept at 26 degrees C. Nutritional status had striking muscle-specific influences on contractile and metabolic properties of myofibres, and especially on myosin isoform expression. A low food intake upregulated slow MyHC mRNA and protein levels in rhomboideus by 53% (P < 0.01) and 18% (P < 0.05) respectively; effects in longissimus dorsi, soleus and diaphragm were not significant. The oxidative capacity of all muscles increased on the low intake, albeit to varying extents: longissimus dorsi (55%), rhomboideus (30%), soleus (21%), diaphragm (7%). Proportions of slow oxidative fibres increased at the expense of fast glycolytic fibres. These novel findings suggest a critical role for postnatal nutrition in regulating myosin gene expression and muscle phenotype. They have important implications for optimal development of human infants: on a low intake, energetic efficiency will increase and the integrated response to many metabolic and growth hormones will alter, since both are dependent on myofibre type. Mechanisms underlying these changes probably involve complex interactions between hormones acting as nutritional signals and differential effects on their cell membrane receptors or nuclear receptors.

Animals↗
PubMed2000

GP selection of postgraduate education courses has implications for colleagues: messages for course providers and for those writing practice professional development plans.

BACKGROUND: The Department of Health's review of continuing professional development in general practice advocates setting team and individual goals. AIM: To explore how general practitioners (GPs) share learning experiences with colleagues, focusing on how GPs choose courses as one factor influencing sharing. METHOD: Interviews were conducted with 21 GPs using grounded theory methodology. The responses were coded by six researchers from psychology, education, and general practice. RESULTS: Much sharing with colleagues took place, though not always immediately following a course. GP explanations revealed four reasons for course selection that influenced the degree of sharing: 1. Attendance to meet group needs encouraged rapid sharing and could involve course attendance with colleagues. 2. Attendance to enhance 'special interests' could either encourage or inhibit sharing. 3. Attendance in pursuit of 'personal interests' peripheral to general practice did not result in sharing within the primary care team. 4. Attendance to meet personal learning needs did not involve sharing when needs were not currently shared with colleagues. CONCLUSION: Course selection and subsequent sharing have implications for course providers and those writing personal and practice professional development plans.

Curriculum↗
PubMed2000

What can general practice learn from complementary medicine?

Complementary medicine is popular in Britain. This suggests that patients who use complementary medicine believe that there are deficiencies in the care they receive from their general practitioners (GPs). Studies of patients using complementary medicine have shown that these patients are sometimes dissatisfied with the communication skills of conventional doctors, the explanations they give for their illnesses, the dangers of modern drugs, and a perceived lack of holistic care. The patients using complementary medicine trusted their bodies' own healing potential and they generally believed that they had more control over their bodies than those patients who did not use complementary medicine. They particularly valued the longer appointment times usually given by the complementary therapists and also the in-depth discussions of their illnesses. Patients using complementary medicine tended to be those with chronic illnesses and these patients particularly valued the positive approach of, and the psychological support given by, the complementary therapists. General practitioners know that all of these aspects of care are important, but the fact that many of our patients go to complementary therapists to satisfy them should encourage us to look at our own practices to see how we as GPs can fulfill these needs.

Attitude to Health↗
PubMed1999

Acute right ventricular dilatation in response to ischemia significantly impairs left ventricular systolic performance.

BACKGROUND: Right ventricular (RV) dilatation that occurs as a consequence of RV infarction is thought to produce hemodynamic instability by reducing left ventricular (LV) preload and compliance. We hypothesized that these geometric changes may also adversely affect LV systolic performance. METHODS AND RESULTS: Twelve 40-kg pigs were studied. Integrated conductance catheters and micromanometers were placed in both the LV and RV to allow simultaneous recordings of pressure and volume and derivation of indices of contractile function. RV ischemia was induced by balloon occlusion of the proximal right coronary artery (RCA) under 3 conditions: 1) with the pericardium intact, 2) with the pericardium intact and inotropic support, and 3) with the pericardium wide open. With an intact pericardium, RCA occlusion produced a decrease in LV end-diastolic volume associated with a marked decline in the contractile function. With the pericardium open, the same ischemic insult resulted in both LV and RV dilatation, which produced a significantly smaller negative effect on cardiac output (P=0.03), LV systolic pressure (P=0.02), LV preload-recruitable stroke work (P<0. 01), and LV end-systolic pressure-volume relations (P<0.01). Similarly, administration of dobutamine during RCA occlusion decreased the ventricular volume changes and produced a relative improvement in LV contractile performance. CONCLUSIONS: The hemodynamic compromise seen in association with acute RV dilatation within an intact pericardium is partly attributable to impaired LV systolic performance and cannot be wholly ascribed to changes in LV preload or compliance.

Animals↗
PubMed1999

Nicotinic acid adenine dinucleotide phosphate triggers Ca2+ release from brain microsomes.

Mobilization of Ca2+ from intracellular stores is an important mechanism for generating cytoplasmic Ca2+ signals [1]. Two families of intracellular Ca(2+)-release channels - the inositol-1,4, 5-trisphosphate (IP3) receptors and the ryanodine receptors (RyRs) - have been described in mammalian tissues [2]. Recently, nicotinic acid adenine dinucleotide phosphate (NAADP), a molecule derived from NADP+, has been shown to trigger Ca2+ release from intracellular stores in invertebrate eggs [3] [4] [5] [6] and pancreatic acinar cells [7]. The nature of NAADP-induced Ca2+ release is unknown but it is clearly distinct from the IP3- and cyclic ADP ribose (cADPR)-sensitive mechanisms in eggs (reviewed in [8] [9]). Furthermore, mammalian cells can synthesize and degrade NAADP, suggesting that NAADP-induced Ca2+ release may be widespread and thus contribute to the complexity of Ca2+ signalling [10] [11]. Here, we show for the first time that NAADP evokes Ca2+ release from rat brain microsomes by a mechanism that is distinct from those sensitive to IP3 or cADPR, and has a remarkably similar pharmacology to the action of NAADP in sea urchin eggs [12]. Membranes prepared from the same rat brain tissues are able to support the synthesis and degradation of NAADP. We therefore suggest that NAADP-mediated Ca2+ signalling could play an important role in neuronal Ca2+ signalling.

Animals↗
PubMed1999

Formant frequency analysis of children's spoken and sung vowels using sweeping fundamental frequency production.

High-pitched productions present difficulties in formant frequency analysis due to wide harmonic spacing and poorly defined formants. As a consequence, there is little reliable data regarding children's spoken or sung vowel formants. Twenty-nine 11-year-old Swedish children were asked to produce 4 sustained spoken and sung vowels. In order to circumvent the problem of wide harmonic spacing, F1 and F2 measurements were taken from vowels produced with a sweeping F0. Experienced choir singers were selected as subjects in order to minimize the larynx height adjustments associated with pitch variation in less skilled subjects. Results showed significantly higher formant frequencies for speech than for singing. Formants were consistently higher in girls than in boys suggesting longer vocal tracts in these preadolescent boys. Furthermore, formant scaling demonstrated vowel dependent differences between boys and girls suggesting non-uniform differences in male and female vocal tract dimensions. These vowel-dependent sex differences were not consistent with adult data.

Adult↗
PubMed1999

Immunization and protection in pneumococcal otitis media studied in a rat model.

The recent and growing problem of bacterial resistance to common antibiotics has generated great interest in different methods for prevention of infections. The treatment of the pathogens causing upper airway infections and especially acute otitis media (AOM) is especially interesting in this context because these infections are a common cause of prescription of antibiotics all over the world. Both in AOM and recurrent AOM, Streptococcus pneumoniae, the most frequently occurring bacterium is isolated in 30-50% of all AOM attacks. In the last decade, multiresistant S. pneumoniae have emerged as a major problem. Thus, it is important to explore possibilities that immunization may protect against pneumococcal OM. In a well-defined animal model using Sprague-Dawley rats, we have investigated the effects of different routes of immunization with different antigens and whole cells. Together with otomicroscopical evaluation of middle ear (ME) status, samples for bacterial cultivation as well as for studies of histopathological changes have been collected. Antibody titers have been followed during and after pneumococcal AOM by an enzyme-linked immunosorbent assay (ELISA) method.

Animals↗
PubMed1999

Access to and use of out-of-hours services by members of Vietnamese community groups in South London: a focus group study.

BACKGROUND: Communication difficulties, lack of knowledge of services and the appropriateness of services influence access to health care services by black and ethnic minority groups. These problems may be accentuated outside normal working hours. This may be so particularly for those who do not speak English as a first language, as interpreting services across the UK are extremely limited in the out-of-hours period. OBJECTIVE: We aimed to describe the experiences and perceptions of members of the Vietnamese community groups in seeking out-of-hours health services and to identify potential solutions from participants' perspectives. METHOD: This qualitative study used a focus group methodology. Participants were members of three established community groups in the South London boroughs of Southwark and Lewisham. Participants attended six focus groups which were conducted in Cantonese and Vietnamese. RESULTS: Participants did not know about GPs' out-of-hours arrangements. And their access to the range of services normally available was limited. They were unable to communicate with health care professionals or answering services and were unaware of out-of-hours interpreting arrangements. Generally, participants were dependent on other people in gaining access to services. Some participants had used 999 services despite communication problems. Participants' experienced delays in seeking health care services and confusion regarding the medicines and advice given. CONCLUSIONS: Communication difficulties limited knowledge of and access to out-of-hours services for the Vietnamese participants. Direct contact with interpreters in the out-of-hours period was suggested as a means of increasing participants' ability to gain access to services. Health service planners need to be aware of the difficulties experienced by such groups if issues of equity in gaining access to health care services are to be addressed.

Adult↗
PubMed1999

A screen for identifying genes interacting with armadillo, the Drosophila homolog of beta-catenin.

Drosophila Armadillo is a multifunctional protein implicated in both cell adhesion, as a catenin, and cell signaling, as part of the Wingless signal transduction pathway. We have generated viable fly stocks with alterations in the level of Armadillo available for signaling. Flies from one stock overexpress Armadillo and, as a result, have increased vein material and bristles in the wings. Flies from the other stock have reduced cytoplasmic Armadillo following overexpression of the intracellular domain of DE-cadherin. These flies display a wing-notching phenotype typical of wingless mutations. Both misexpression phenotypes can be dominantly modified by removing one copy of genes known to encode members of the wingless pathway. Here we describe the identification of further mutations that dominantly modify the Armadillo misexpression phenotypes. These mutations are in genes encoding three different functions: establishment and maintenance of adherens junctions, cell cycle control, and Egfr signaling.

Animals↗
PubMed1999

Nonsegmental ventilation-perfusion scintigraphy mismatch after radiation therapy.

PURPOSE: This report illustrates the utility of ventilation-perfusion scintigraphy in differentiating radiation pneumonitis from other causes of dyspnea, including pulmonary embolism, heart failure, obstructive tumor, and chronic obstructive pulmonary disease. METHODS AND RESULTS: A nonsegmental mismatched perfusion abnormality, which exactly conformed to a radiation port, was diagnostic of radiation pneumonitis. CONCLUSION: In patients with lung tumors presenting with dyspnea, ventilation-perfusion scintigraphy may be useful in diagnosing radiation pneumonitis and effectively excluding other causes of dyspnea.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients.

OBJECTIVE: To assess the safety and potential efficacy of a mechanical ventilation strategy designed to reduce stretch-induced lung injury in acute respiratory distress syndrome. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Eight intensive care units in four teaching hospitals. PATIENTS: Fifty-two patients with acute respiratory distress syndrome. INTERVENTIONS: Traditional tidal volume patients: tidal volume 10-12 mL/kg ideal body weight, reduced if inspiratory plateau pressure was > 55 cm H2O (7.3 kPa). Small tidal volume patients: tidal volume 5-8 mL/kg ideal body weight, to keep plateau pressure < 30 cm H2O (4.0 kPa). MEASUREMENTS AND MAIN RESULTS: Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg, respectively (p < .001), with mean plateau pressure = 30.6 and 24.9 cm H2O (3.3 kPa), respectively (p < .001). There were no significant differences in requirements for positive end-expiratory pressure or FIO2, fluid intakes/outputs, requirements for vasopressors, sedatives, or neuromuscular blocking agents, percentage of patients that achieved unassisted breathing, ventilator days, or mortality. CONCLUSIONS: The reduced tidal volume strategy used in this study was safe. Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a) the sample size was too small to discern small treatment effects; b) the differences in tidal volumes and plateau pressures were modest; or c) reduced tidal volume ventilation is not beneficial.

Adult↗
PubMed1999

Inhibition of nitric oxide synthesis improves left ventricular contractility in neonatal pigs late after cardiopulmonary bypass.

BACKGROUND: Following neonatal open heart surgery a nadir occurs in left ventricular function six to 12 hours after cardiopulmonary bypass. Although initiated by intraoperative events, little is known about the mechanisms involved. OBJECTIVE: To evaluate the involvement of nitric oxide in this late phase dysfunction in piglets. DESIGN: Piglets aged 2 to 3 weeks (4-5 kg) underwent cardiopulmonary bypass (1 h) and cardioplegic arrest (0.5 h) and then remained ventilated with inotropic support. Twelve hours after bypass, while receiving dobutamine (5 microg/kg/min), the left ventricular response to non-selective nitric oxide synthase inhibition (l-N(G)-monomethylarginine (l-NMMA)) was evaluated using load dependent and load independent indices (E(es), the slope of the end systolic pressure-volume relation; M(w), the slope of the stroke work-end diastolic volume relation; [dP/dt(max)](edv), the slope of the dP/dt(max)-end diastolic volume relation), derived from left ventricular pressure-volume loops generated by conductance and microtip pressure catheters. RESULTS: 10 pigs received 7.5 mg l-NMMA intravenously and six of these received two additional doses (37.5 mg and 75 mg). E(es) (mean (SD)) increased with all three doses, from 54.9 (40.1) mm Hg/ml (control) to 86.3 (69.5) at 7.5 mg, 117.9 (65.1) at 37.5 mg, and 119 (80.4) at 75 mg (p < 0.05). At the two highest doses, [dP/dt(max)](edv) increased from 260.8 (209.3) (control) to 470.5 (22.8) at 37.5 mg and 474.1 (296.6) at 75 mg (p < 0.05); and end diastolic pressure decreased from 16.5 (5.6) mm Hg (control) to 11.3 (5.0) at 37.5 mg and 11.4 (4.9) at 75 mg (p < 0. 05). CONCLUSIONS: In neonatal pigs 12 hours after cardiopulmonary bypass with ischaemic arrest, low dose l-NMMA improved left ventricular function, implying that there is a net deleterious cardiac action of nitric oxide at this time.

Animals↗