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Biomedical subjects

R Gray

Publications and source records attributed to R Gray.

At least 127 records · Page 7Linked to original sources
PubMed1999

Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group.

PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.

Adult↗
PubMed1999

Motion in depth: adequate and inadequate simulation.

We measured errors in estimating the absolute time to collision with a simulated approaching textured object. The texture elements were circular bright dots. When we matched the rate of angular expansion of the simulated object, the rate of expansion of the texture dots, and the rate of increase of dot separation, so as to accurately simulate an approaching object, errors were small underestimations that were independent of dot size (mean of 3.2%). When dot angular size was held constant during the simulated approach, errors were the same as when the simulation was accurate, provided that dot size was less than 2.2-4.4 min of arc. As dot size was progressively increased, errors changed to overestimations. For the largest dot size used (10.5 min of arc at time t = 0), time to collision was overestimated by up to 21%. A sufficiently large overestimation would mean that measures taken to avoid collision would be too late. We suggest that the relevance to everyday life of data on the perception of motion in depth and self-motion collected using constant-sized dot displays might be questionable if dot size exceeds 2.2-4.4 min of arc.

Adult↗
PubMed1999

Survivors' perspectives on the impact of prostate cancer: implications for oncology nurses.

Providing effective care for individuals with prostate cancer is an important issue for oncology nurses. However, the paucity of empirical work regarding the impact of prostate cancer presents a limitation in designing and implementing appropriate nursing interventions. This article presents the findings from a national survey of 621 Canadian men living with prostate cancer regarding the impact of their disease and the availability of support. The most frequently identified problems included sexual function, side effects, fear of dying, incontinence, anger and pain. Approximately one-third of the respondents experienced a lifestyle change, but relatively few indicated experiencing a negative impact from the changes they experienced. The majority of respondents indicated they had been informed accurately about their treatment, but dissatisfaction was expressed regarding lack of information about emotional reactions, alternative therapies, how to speak with other prostate cancer patients and the availability of counselling and self-help groups. Clearly these results have implications for oncology nurses.

Adaptation, Psychological↗
PubMed1998

Quantification of effects of global ischemia on dynamics of ventricular fibrillation in isolated rabbit heart.

BACKGROUND: Ventricular fibrillation (VF) leads to global ischemia of the heart. After 1 to 2 minutes of onset, the VF rate decreases and appears more organized. The objectives of this study were to determine the effects of no-flow global ischemia on nonlinear wave dynamics and establish the mechanism of ischemia-induced slowing of the VF rate. METHODS AND RESULTS: Activation patterns of VF in the Langendorff-perfused rabbit heart were studied with the use of 2 protocols: (1) 15 minutes of no-flow global ischemia followed by reperfusion (n=7) and (2) decreased excitability induced by perfusion with 5 micromol/L of tetrodotoxin (TTX) followed by washout (n=3). Video imaging ( approximately 7500 pixels per frame; 240 frames per second) with a voltage-sensitive dye, ECG, and signal processing (fast Fourier transform) were used for analysis. The dominant frequency of VF decreased from 13.5+/-1.3 during control to 9.3+/-1.4 Hz at 5 minutes of global ischemia (P<0.02). The dominant frequency decreased from 13.9+/-1.1 during control to 7.0+/-0.3 Hz at 2 minutes of TTX infusion (P<0.001). The rotation period of rotors on the epicardial surface (n=27) strongly correlated with the inverse dominant frequency of the corresponding episode of VF (R2=0. 93). The core area, measured for 27 transiently appearing rotors, was 5.3+/-0.7 mm2 during control. A remarkable increase in core area was observed both during global ischemia (13.6+/-1.7 mm2; P<0.001) and TTX perfusion (16.8+/-3.6 mm2; P<0.001). Density of wave fronts decreased during both global ischemia (P<0.002) and TTX perfusion (P<0.002) compared with control. CONCLUSIONS: This study suggests that rotating spiral waves are most likely the underlying mechanism of VF and contribute to its frequency content. Ischemia-induced decrease in the VF rate results from an increase in the rotation period of spiral waves that occurs secondary to an increase in their core area. Remarkably, similar findings in the TTX protocol suggest that reduced excitability during ischemia is an important underlying mechanism for the changes seen.

Animals↗
PubMed1998

Accuracy of estimating time to collision using binocular and monocular information.

We measured both the just-noticeable difference in time to collision (TTC) with an approaching object, and the absolute accuracy in estimating TTC in the following cases: only binocular information available; only monocular information available; both binocular and monocular information available as in the everyday situation. Observers could discriminate trial-to-trial variations in TTC on the basis of binocular information alone: the just-noticeable difference in TTC (5.1-9.8%) was the same for a small (0.03 deg) target and for a large (0.7 deg) target. In line with previous reports, when only monocular information was available, the just-noticeable difference in TTC was 5.8-12% for the large target. However, observers could not reliably discriminate trial-to-trial variations in TTC with the small target when only monocular information was available. When both binocular and monocular information was available, the just-noticeable difference in TTC for the large target was not significantly different from when only binocular or only monocular information was available. Observers could make reliable estimates of absolute TTC using binocular information only. Errors ranged from 2.5 to 10% for the large target, and 2.6 to 3.0% for the small target, all being overestimates. Errors for the small target were the same or lower than errors for the large target. Observers could make reliable estimates of TTC with the large target using monocular information only. Errors ranged from 2.0 to 12%, all being underestimates. Since monocular information did not provide a basis for reliable estimates of absolute TTC with the small target we conclude that, in everyday conditions, accurate estimates of TTC with small targets are based on binocular information when the object is small and is no more than a few metres away. Errors in estimating absolute TTC were lower in the case where both binocular and monocular information were available (as in the everyday situation) than when only binocular information or only monocular information was available. Errors ranged from 1.3 to 2.7%. An error of 1.3% approaches the accuracy required to explain the +/- 2.0-2.5 msec accuracy with which top sports players can estimate the instant of impact between bat and ball.

Depth Perception↗
PubMed1998

Spatial frequency discrimination and detection characteristics for gratings defined by orientation texture.

We describe evidence consistent with the proposal that the visual system contains a parallel array of size-tuned mechanisms sensitive to orientation texture-defined (OTD) form, and propose that the relative activity of these mechanisms determines spatial frequency discrimination threshold for OTD gratings. Using a pattern of short lines we measured spatial frequency discrimination thresholds for OTD gratings and luminance-defined (LD) gratings. For OTD gratings, the orientation of texture lines varied sinusoidally across the bars of the gratings, but line luminance was constant. For LD gratings, line orientation was constant, but line luminance varied sinusoidally across the bars of the grating. When the number of texture lines (i.e. spatial samples) per grating cycle was below about six, spatial sampling strongly affected both the spatial frequency discrimination and grating detection thresholds for OTD and LD gratings. However, when the number of spatial samples per grating cycle exceeded about six, plots of both discrimination threshold and detection threshold were different for OTD and LD gratings. For an OTD grating of any given spatial frequency, spatial frequency discrimination threshold fell as the number of samples per grating cycle was increased while holding texture line length constant: the lower limit was reached at six to ten samples per cycle. When we progressively increased the viewing distance (keeping the cycles per degree (cpd) constant), spatial frequency discrimination threshold reached a lower limit and increased thereafter. We propose that this minimum threshold represents a balance between opposing effects of the number of samples per grating cycle and the length of texture lines, and approaches the absolute physiological lower limit for OTD gratings. Spatial frequency discrimination was possible up to at least 7 cpd. Grating acuity for an OTD grating was considerably lower than the physiological limit for LD gratings, presumably because detectors of OTD form include a spatial integration stage following the processing of individual lines. For an LD grating, discrimination threshold fell as the number of samples per grating cycle was increased and asymptoted at six to ten samples per cycle. Spatial frequency discrimination thresholds for OTD and LD gratings were similar at low spatial frequencies (up to 3-4 cpd), but increased more steeply for OTD gratings at high spatial frequencies. For both OTD and LD gratings, discrimination threshold fell steeply as the number of grating cycles was increased from 0.5 to ca. 2.5 cycles, and thereafter decreased more slowly or not at all suggesting that, for both OTD and LD gratings, spatial frequency discrimination can be regarded as a special case of line interval or bar width discrimination. As orientation contrast was progressively increased, discrimination threshold for an OTD grating fell steeply up to about four to five times grating detection threshold, then saturated. This parallels the effect of luminance contrast on discrimination threshold for an LD grating.

Adult↗
PubMed1998

Phase II study of CI-980 (NSC 635370) in patients with previously treated advanced soft-tissue sarcomas.

Doxorubicin and ifosfamide are the two most active agents in the treatment of soft-tissue sarcomas. Patients whose tumors have failed these two drugs have very limited systemic therapy options. It is, therefore, important to identify newer drugs with activity against this disease. CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site and inhibits the polymerization of tubulin and blocks cell cycle progression in mitosis. Given its broad spectrum activity against several solid tumor models in vivo, we decided to perform a phase 2 study of this drug in previously treated soft-tissue sarcomas. A total of 18 eligible and evaluable patients were entered in the first stage of the trial. The median age was 53 yrs (range, 17-72). No objective responses have been noted. Six patients had stable disease after a median of 3.5 cycles of chemotherapy while 12 others had progressive disease. A total of 48 cycles were administered, 42 of which were administered at dose level 0 (4.5 mg/m2/d x 3). The median AGC nadir was 1.2/microl(0.1 -4.7) on day 10 and the median platelet nadir was 150,000/microl (31,000-338,000). Twenty cycles were complicated with grade 3-4 neutropenia and two cycles were complicated with FUO. There were no CNS toxicities. One patient had a grade 1 thrombophlebitis in 2 cycles and one other patient had a grade 4 thrombophlebitis in one cycle. In conclusion, CI-980 was well tolerated at this dose and schedule but inactive in soft-tissue sarcomas.

Adolescent↗
PubMed1998

Effects of four years' treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH-deficient adults.

OBJECTIVE: To study the effects of long-term growth hormone (GH) treatment on lipid metabolism and carbohydrate tolerance in GH-deficient adults. DESIGN: Open trial of GH treatment for 4 years. GH dose was (median, range) 0.025 (0.010-0.050) IU/kg daily. PATIENTS: Thirteen GH-deficient hypopituitary adults (seven men, six women), aged (median, range) 47 (24-65) years were followed for 4 years. MEASUREMENTS: Fasting lipids, lipoproteins, apolipoproteins, glucose and insulin concentrations were measured at yearly intervals during GH therapy. A 75-g oral glucose tolerance test (OGTT) was also performed yearly, during which circulating glucose and insulin were measured at 30-minute intervals for 3 h. RESULTS: Fasting total and low density lipoprotein (LDL) cholesterol concentrations decreased on GH therapy, but no change was observed in fasting triglyceride or high density lipoprotein (HDL) concentrations. Compared to pretreatment values, total and LDL cholesterol levels were significantly lower at 1 year (mean +/- SEM) (6.39 +/- 0.46 vs. 5.71 +/- 0.38 mmol/l, P < 0.05; 4.46 +/- 0.36 vs. 3.24 +/- 0.20 mmol/l, P < 0.01, respectively) and the reductions were maintained for the 4 years. Apolipoproteins A-1 and B did not differ significantly from the pretreatment levels. Fasting plasma glucose increased significantly at the first year (4.9 +/- 0.1 vs. 5.3 +/- 0.1 mmol/l, P < 0.05) but it returned to the pretreatment value in the following years. Fasting plasma insulin increased significantly at 1 year (4.3 (1.0-13.6) vs. 11.9 (1.2-26.9) mU/l, P < 0.05) and showed a progressive downward trend but remained significantly raised throughout the subsequent years. The 3-h area under the glucose curve (AUC) during the OGTT tended to be increased at the first year (P = 0.07) and it returned to the pretreatment level in the following years. The AUC of plasma insulin was significantly raised at 1 year (P = 0.024) and it returned to the pretreatment level in the following years. CONCLUSIONS: Four years of GH therapy in GH-deficient adults resulted in a sustained improvement in total and LDL cholesterol concentrations. Mild fasting hyperinsulinaemia persisted, although an initial deterioration in glucose tolerance, associated with post-glucose hyperinsulinaemia, was not sustained.

Adult↗
PubMed1998

Asymptomatic non-ulcerative genital tract infections in a rural Ugandan population.

OBJECTIVE: To document the prevalence of asymptomatic non-ulcerative genital tract infections (GTI) in a rural African cohort. METHODS: The study population consisted of all adults aged 15-59 residing in 56 rural communities of Rakai District, southwest Uganda, enrolled in the Rakai STD Control for AIDS Prevention Study. Participants were interviewed about the occurrence of vaginal or urethral discharge and frequent or painful urination in the previous 6 months. Respondents were asked to provide blood and a first catch urine sample. Serum was tested for HIV-1. Urine was tested with ligase chain reaction (LCR) for N gonorrhoeae and C trachomatis. Women provided two self administered vaginal swabs; one for T vaginalis culture and the other for a Gram stained slide for bacterial vaginosis (BV) diagnosis. RESULTS: A total of 12,827 men and women were enrolled. Among 5140 men providing specimens, 0.9% had gonorrhoea and 2.1% had chlamydia. Among 6356 women, 1.5% had gonorrhoea, 2.4% had chlamydia, 23.8% were infected with trichomonas and 50.9% had BV.53% of men and 66% of women with gonorrhoea did not report genital discharge or dysuria at anytime within the previous 6 months. 92% of men and 76% of women with chlamydia and over 80% of women with trichomonas or BV were asymptomatic. The sensitivities of dysuria or urethral discharge for detection of infection with either gonorrhoea or chlamydia among men were only 21.4% and 9.8% respectively; similarly, among women the sensitivity of dysuria was 21.0% while that of vaginal discharge was 11.6%. For trichomonas or BV the sensitivity of dysuria was 11.7% and that of vaginal discharge was 10.5%. CONCLUSION: The prevalence of non-ulcerative GTIs is very high in this rural African population and the majority are asymptomatic. Reliance on reported symptoms alone would have missed 80% of men and 72% of women with either gonorrhoea or chlamydia, and over 80% of women with trichomonas or BV. To achieve STD control in this and similar populations public health programmes must target asymptomatic infections.

Adolescent↗
PubMed1998

L-Type calcium channels are required for one form of hippocampal mossy fiber LTP.

The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 +/- 5% (mean +/- SE) increase in control versus 7 +/- 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 +/- 10% in control vs. 80 +/- 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl--aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.

Animals↗