Biomedical subjects
R Wilson
Publications and source records attributed to R Wilson.
Screening-detected and symptomatic ductal carcinoma in situ: mammographic features with pathologic correlation.
PURPOSE: To compare the mammographic and pathologic features of screening-detected and symptomatic ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: The mammographic and pathologic features of 54 screening-detected and 77 symptomatic cases of DCIS were compared. Patients were aged 30-76 years (mean, 58 years). RESULTS: Diffuse involvement was seen in 10 patients (13%) with symptoms but in none of the screening-detected group (P < .05). The disease was radiologically more extensive in the symptomatic group. Calcifications in the symptomatic group (n = 48) were less likely to have a ductal distribution than those in the screening-detected group (n = 48) (30 [63%] vs 40 [83%], respectively; P < .05). At histologic examination in some cases, the symptomatic group (n = 76) included eight (11%) patients with cribriform-micropapillary, large-cell tumors (P < .05) and less comedocarcinoma (20 [26%] vs 23 [45%], respectively; P < .05) compared with the screening-detected group (n = 51). CONCLUSION: The results show differences in the radiologic and pathologic features of screening-detected and symptomatic DCIS.
Acute adaptation of carbohydrate metabolism to decreased arterial PO2.
To assess the interaction of arterial PO2 (PaO2) and glucose metabolism, conscious 18-h-fasted dogs with chronically implanted sampling catheters (carotid artery, iliac vein) and flow probe (external iliac artery) were studied during inspiration of air containing 21 (n = 9), 14 (n = 6), 11 (n = 4), or 8% (n = 5) O2. Isotopic and arteriovenous methods were used to assess carbohydrate metabolism. PaO2 was 103 +/- 3, 64 +/- 4, 45 +/- 4, and 30 +/- 1 mmHg with decreased inspired O2. Although limb O2 delivery was reduced (51 +/- 6, 42 +/- 8, 39 +/- 7, and 34 +/- 5 ml/min), limb O2 uptake was not compromised. Plasma insulin was 9 +/- 1, 8 +/- 2, 14 +/- 2, and 16 +/- 3 microU/ml, and glucagon was 53 +/- 3, 49 +/- 3, 64 +/- 5, and 101 +/- 7 pg/ml with decreasing O2. Plasma epinephrine and cortisol were increased whereas norepinephrine was unaffected. Glycemia was unaffected by reduced O2, whereas hepatic glucose output (14 +/- 1, 19 +/- 3, 21 +/- 1, and 22 +/- 1 mumol.kg-1.min-1) and glucose disappearance (14 +/- 2, 18 +/- 3, 20 +/- 1, and 22 +/- 2 mumol.kg-1.min-1) rose similarly. Limb glucose uptake (LGU) rose (21.5 +/- 4.7, 21.2 +/- 5.6, 30.6 +/- 4.7, and 45.3 +/- 9.7 mumol/min) with decreasing O2 because of greater fractional extraction (0.023 +/- 0.005, 0.024 +/- 0.005, 0.031 +/- 0.004, and 0.043 +/- 0.004). Of the increased LGU, approximately 33 and 67% were metabolized oxidatively and nonoxidatively.(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction of Pseudomonas aeruginosa with human respiratory mucosa in vitro.
Pseudomonas aeruginosa commonly infects the airways of patients with cystic fibrosis and bronchiectasis. It produces several toxins that slow ciliary beat, stimulate mucus production and damage epithelium. It adheres to epithelial cells, damaged mucosa (in animal models), and mucus. However, little is known of the interaction of P. aeruginosa with intact human respiratory mucosa. We have studied the interactions of a nonmucoid clinical isolate of P. aeruginosa with adenoid tissue in a novel organ culture model with an air-mucosal interphase P. aeruginosa (5.9 +/- 0.9 x 10(6) colony-forming units (cfu)) was pipetted onto the organ culture surface, and incubated for 15 min, 1, 2, 4, 8, 12, 16, and 24 h, at 37 degrees C in 5% CO2 in a humidified atmosphere. Assessment has been made by transmission and scanning electron microscopy. Transmission electron microscopy (TEM) showed that uninfected organ cultures had normal ultrastructure. TEM of infected organ cultures at 8 h showed significant epithelial damage: 43.9 +/- 10% of cells extruding from the epithelial surface, 17.7 +/- 3% of cells with loss of cilia, 32.9 +/- 10.2% of cells with mitochondrial damage, and 11.6 +/- 3% of cells with cytoplasmic blebbing. P. aeruginosa only infrequently adhered to normal epithelium, but adhered to areas of epithelial damage and to basement membrane. Scanning electron microscopy (SEM) of organ cultures up to 2 h found P. aeruginosa only infrequently associated with mucus. SEM at 4 h revealed P. aeruginosa predominantly associated with mucus and extruded damaged epithelial cells, but also occasionally associated with cilia, and very occasionally with unciliated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Impaired memory and behavioral performance with fentanyl at low plasma concentrations.
Fentanyl is commonly administered to conscious patients by continuous epidural or intravenous (i.v.) infusions, or by the transdermal route, which result in relatively constant, low, concentrations of the drug. Previous studies of memory and cognitive effects have not been performed at constant plasma concentrations of fentanyl. Based on simulated infusions using the pharmacokinetic modeling program IV-SIM, we administered fentanyl or placebo to nine healthy volunteers (aged 21-45 yr) by continuous i.v. infusion, targeting plasma concentrations of 1, 1.5, and 2.5 ng/mL in succession. A battery of memory and psychomotor tasks was administered at each plasma concentration of fentanyl, and at two points in the recovery phase while drug levels were decreasing. At increasing plasma concentrations of fentanyl, we found the following effects on memory (in comparison with placebo): a progressive decline in verbal learning (P < 0.03); decreased delayed recognition of words presented at different test times (P < 0.02); and decreased spontaneous recall of pictures shown during infusion (P < 0.03). Fentanyl at concentrations above 2.5 ng/mL caused a performance decrement of 15%-30% relative to baseline on all the psychomotor tests administered. Plasma concentrations less than 2.25 ng/mL had negligible effects on performance with the exception of the critical flicker fusion frequency, which decreased by 5 Hz at plasma concentrations between 1.5 and 2.25 ng/mL. Visual analog scale (VAS) measures of mental and physical sedation were significantly affected by fentanyl, but euphoria was not demonstrable. All subjects receiving fentanyl experienced severe nausea and four of six had one or more episodes of emesis (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
AMMONIA EXCRETION IN FRESHWATER RAINBOW TROUT (ONCORHYNCHUS MYKISS) AND THE IMPORTANCE OF GILL BOUNDARY LAYER ACIDIFICATION: LACK OF EVIDENCE FOR Na+/NH4+ EXCHANGE
Net ammonia fluxes (JAmm) were measured in adult freshwater rainbow trout in vivo under a variety of conditions designed to inhibit unidirectional sodium uptake (JinNa; low external [NaCl], 10(-4) mol l-1 amiloride), alter transbranchial PNH3 and NH4+ gradients [24 h continuous (NH4)2SO4 infusion, or exposure to 1 mmol l-1 external total ammonia at pH 8] and prevent gill boundary layer acidification (5 mmol l-1 Hepes buffer). Inhibition of JinNa with amiloride or low external [NaCl] under normal conditions reduced JAmm by about 20 %, but did not prevent the net excretion of ammonia during exposure to high concentrations of external ammonia. Increasing the buffer capacity of the ventilatory water with Hepes buffer (pH 8) reduced JAmm by 36 % and abolished the effect of amiloride on ammonia excretion. No evidence could be found to support a directly coupled apical Na+/NH4+ exchange. We suggest that any dependence of ammonia excretion on sodium uptake is caused by alteration of transbranchial PNH3 gradients within the gill microenvironment secondary to changes in net H+ excretion. Under normal conditions (pH 8, low external ammonia) gill boundary layer acidification facilitates over one-third of the total ammonia excretion. During exposure to high concentrations of external ammonia in poorly buffered water, estimates of transbranchial PNH3 gradients from measurements of bulk water pH and total ammonia concentration (TAmm) may be grossly in error because of boundary layer acidification. Prevention of boundary layer acidification with Hepes buffer during exposure to high cocncentrations of external ammonia revealed that the local transbranchial PNH3 gradient at the gill may in fact be positive (blood to water), negating the need for an active NH4+ transport mechanism. In freshwater trout, NH3 diffusion may account for all ammonia excretion under all experimental conditions used in the present study.
ASSESSMENT OF MAXIMUM SUSTAINABLE SWIMMING PERFORMANCE IN RAINBOW TROUT (ONCORHYNCHUS MYKISS)
Levels of swimming activity in fishes have been divided into three categories on the basis of the time a given speed can be maintained before the onset of fatigue (Beamish, 1978): sustained (more than 200 min), prolonged (20 s to 200 min) and burst swimming (less than 20 s). The locomotory capacity of a given species reflects both its lifestyle and its body form, although definitions of performance may vary. It is generally accepted that only the aerobic ('red') muscle fibres should be active at truly sustainable swimming speeds, i.e. at speeds that can be maintained indefinitely without fatigue. However, the standard laboratory method of evaluating the maximum sustainable swimming speed (Ucrit; Brett, 1964) almost certainly entails the recruitment of at least some of the rapidly fatigable fast glycolytic ('white') fibres at sub-critical speeds and undoubtedly complicates the evaluation of maximal cardiovascular performance. It would therefore be useful to have an objective and reproducible measure of truly sustainable performance that, by definition, relies solely on aerobic muscle activity. Electromyography (EMG) has been used to examine the pattern of white muscle recruitment following thermal acclimation in striped bass, Morine saxatilis (Sisson and Sidell, 1987). We wished to incorporate this method into a study of the acclimatory responses to chronic changes in environmental temperature of the cardiovascular and locomotory systems in rainbow trout (Wilson and Egginton, 1992). The present communication presents results on the cardiovascular performance and blood chemistry, at rest and during maximal aerobic exercise, of rainbow trout acclimated to 11 °C, as a validation of the methodology currently in use with fish acclimated to seasonal temperature extremes (Taylor et al. 1992). Different acclimation temperatures are known to produce compensatory changes in the relative proportions of red and white muscle mass (Sidell and Moerland, 1989). The aim of these continuing investigations is to compare the anatomical, cardiovascular and locomotory limitations to aerobic exercise over the full temperature range of a eurythermal fish species.
HYDRODYNAMIC ASPECTS OF DESIGN AND ATTACHMENT OF A BACK-MOUNTED DEVICE IN PENGUINS
Wind tunnel and water tank experiments were carried out on a penguin model in order to optimise the shape and attachment of a back-mounted datalogger. Device-induced turbulence was minimised when the unit was placed in the most caudal position. Drag was further reduced by shaping the device to match the body contour. The hydrodynamic resistance of the package could be reduced by 65 % compared with an earlier unit. These results are discussed together with results from new studies on kinematics and energetics of underwater swimming of live instrumented penguins.
UNDERWATER SWIMMING AT LOW ENERGETIC COST BY PYGOSCELID PENGUINS
Energetic requirements of under-water swimming in pygoscelid penguins were studied in Antarctica, using respirometry together with a 21 m long swim canal and externally attached devices recording the swimming speed and dive duration of unrestrained animals. Field measurements were compared with measurements of the hydrodynamic properties of an Adelie penguin model in a circulating water tank. Minimium transport costs during underwater swimming in Adelie (Pygoscelis adeliae), chinstrap (P. antarctica) and gentoo (P. papua) penguins averaged 4.9, 3.7 and 7.6 J kg-1 m-1, respectively, at their preferred swimming speeds of 2.2, 2.4 and 1.8 m s-1, allowing the birds to dive aerobically for 110, 130 and 93 s, respectively. From the swim canal measurements, we calculated a drag coefficient (CD) of 0.0368 for a typical Adelie penguin at 2.2 m s-1. This value is significantly lower than the CD of 0.04 of an ideal spindle and the CD of 0.0496 measured on the model in the laboratory. The reasons for this difference are discussed.
Ductal carcinoma in situ of the breast: correlation between mammographic and pathologic findings.
OBJECTIVE: Ductal carcinoma in situ shows heterogeneous clinical behavior and response to treatment depending on its pathologic features. The aim of this study was to correlate the radiologic and pathologic features of ductal carcinoma in situ of the breast. Differences, if present, may allow refinement of diagnosis and selection of treatment options. MATERIALS AND METHODS: The mammograms of 128 patients with ductal carcinoma in situ of the breast were analyzed by a radiologist who knew that the patients had ductal carcinoma in situ but had no other pathologic information. The radiologic and pathologic features of subgroups characterized according to cell size and presence of necrosis were then compared. Statistical comparisons were made by using the chi 2- and Fisher's exact tests. RESULTS: Patients with small-cell ductal carcinoma in situ more commonly have a normal mammogram (28% vs 6%, respectively, p < .001) or an abnormal mammogram without calcification (42% vs 5%, respectively, p < .001) than do patients with large-cell ductal carcinoma in situ. Among patients with abnormal mammographic findings, calcification is present in 58% of those with small-cell ductal carcinoma in situ, compared with 95% of those with large-cell ductal carcinoma in situ (p < .001). No significant differences were found in the calcification morphology of small- and large-cell ductal carcinoma in situ. These features were seen more commonly in ductal carcinoma in situ with necrosis than in ductal carcinoma in situ without necrosis, respectively: abnormal mammographic findings (95% vs 73%, p < .001), calcification (96% vs 61%, p < .001), calcification with a ductal distribution (80% vs 45%, p < .005), and rod-shaped calcification (83% vs 45%, p < .001). An abnormal mammogram without calcification (39% vs 4%, p < .001) or predominantly punctate calcification (36% vs 13%, p < .05) was seen more commonly in ductal carcinoma in situ without necrosis than in ductal carcinoma in situ with necrosis, respectively. CONCLUSION: We have shown that the radiologic features of ductal carcinoma in situ vary according to cell size and the presence of necrosis in particular. Necrosis has been found to be a feature of more biologically aggressive in situ breast cancer, so these findings may be of practical value in deciding the management of indeterminate calcification clusters and whether to offer breast conservation.
The role of cytokines in the production of prostacyclin and thromboxane in human mononuclear cells.
The aim of the present work was to study the regulatory effects of cytokines (TNF alpha, IL-1 beta and IL-2) on the production of the prostglandins (PGI2 and TXA2) from human mononuclear cells. Our major findings were: (1) TNF alpha, IL-1 beta and IL-2 were all able to induce PGI2 and TXA2 syntheses in mononuclear cells. (2) TNF alpha exerted a biphasic effect on prostaglandin production. The lower concentrations of TNF alpha enhanced prostaglandin synthesis while the higher concentrations did not. (3) TNF alpha had a positive effect after only a 30-minute incubation, whereas IL-1 beta and IL-2 required a 8-hour incubation to produce a significant effect. This suggests that the different mechanisms are involved in their actions. (4) The effects of cytokines on the production of PGI2 were greater than that on the production of TXA2. It is concluded that cytokines can not only regulate the production of prostaglandins but also change the pattern of their formation.
B cell number and function in Graves' disease.
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Normal superoxide dismutase (SOD) gene in pregnancy-induced hypertension: is the decreased SOD activity a secondary phenomenon?
Reactive oxygen species (ROS) have been implicated in the pathogenesis of pregnancy-induced hypertension (PIH). A genetic factor is also thought to be associated with the disease. The aim of the present study was to investigate whether decreased superoxide dismutase (SOD) activity in PIH resulted from gene abnormalities. Fourteen patients with PIH were enrolled in the study. Normal pregnant women and normal nonpregnant women served as controls. Genomic DNA and mRNA were isolated from white cells and subjected to Southern and Northern blot analysis with a 600 bp CuZn-SOD probe. SOD activity was also determined in the white blood cells and red blood cells. The results showed that SOD activity was significantly reduced in patients with PIH compared to both control groups. There were no significant differences in the size of the CuZn-SOD gene and its expression between the patients with PIH and the controls. This study confirmed that there was a decreased SOD activity in PIH but revealed neither major structural changes in the genomic DNA nor mRNA size of CuZn-SOD. Our results suggest that the decreased SOD levels in PIH are not due to abnormalities in the CuZn-SOD gene and are an acquired phenomenon which occurs during the development of the disease.
Evaluation of the Plazlyte Sterilization System at the Richmond Hospital, Richmond, B.C.
Ethylene oxide mixed with chlorofluorocarbons has been the sterilant of choice for heat- and pressure-sensitive instruments and equipment in most Canadian and U.S. healthcare facilities. A pending July 1, 1994 ban on CFCs in British Columbia propelled the Greater Vancouver Regional Hospital District (GVRHD) to seek out any new available technologies to replace EtO sterilization. AbTox Plazlyte Sterilization System, which employs a proprietary, low-temperature gas plasma in conjunction with vaporized peracetic acid chemistry to provide terminal sterilization of instruments and devices, appeared very promising. A task force was formed at the Richmond Hospital to develop and implement a clinical isolate test protocol of the system. Following the three-month trial, the results showed the system to be effective in sterilizing all clinical isolates and compatible with the materials tested. There has also been improved product throughput. The Richmond Hospital now uses one Plazlyte sterilizer to process all items formerly processed using EtO.
Current issues in the selection and use of broad-spectrum antibiotics. Roundtable discussion.
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Kaiser Permanente: green and growing.
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Medical and dental staffing prospects in the NHS in England and Wales 1993.
This article provides a brief update on current national policies affecting medical education and training, and information on the present medical and dental workforce. Although of general interest, senior medical students and doctors in the training grades may find it particularly helpful when considering choices of future career. As there may be marked local variations in career prospects for any one specialty, further information and advice is available from Regional Postgraduate Medical and Dental Deans, specialty advisors (through Royal College and specialty associations) and clinical tutors. The information in this article relates to the present situation only and a review of previous articles in this series may be useful to observe certain trends.
Toward equity in health research.
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