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Biomedical subjects

R Gray

Publications and source records attributed to R Gray.

At least 217 records · Page 12Linked to original sources
PubMed1993

High DNA content and prognosis in lymph node positive breast cancer. A case control study by the University of Leiden and ECOG. (Eastern Cooperative Oncology Group).

To investigate whether breast cancer cells with unusually high nuclear DNA content are associated with an adverse outcome, Eastern Cooperative Oncology Group investigators selected breast cancer trial patients who suffered an early death (ED) within two years after diagnosis to compare with other trial patients who had a survival of at least 7.5 years. Paraffin blocks of primary breast cancers were obtained from 93 evaluable patients who had been enrolled in two surgical adjuvant trials for lymph node positive (LN+) disease (T1-3N1M0). Single cell monolayer preparations from these blocks were stained with acriflavine-Feulgen and analyzed by image analysis for DNA content with the automated Leiden Television Analysis System (LEY-TAS). Standard prognostic variables (estrogen receptor (ER) status, number of lymph nodes with metastases, and size of the cancer) were compared with three DNA content characteristics: DNA ploidy status, number of nuclei with > 5C DNA content, and percent of nuclei with > 5 C. Estimates of the odds ratio in multivariate comparisons showed that ER negativity was associated with ED (p = 0.0005) and an odds ratio estimate using negative/positive of 4.87. The number of positive lymph nodes associated with ED had a p-value of 0.0005 and an odds ratio estimate of 4.63 when comparing the > 3 nodes group to the 1-3 nodes group. In contrast, the strongest association for any of the DNA content characteristics with ED had a p-value of 0.017 and an odds ratio estimate of 2.76. This power of association disappeared when stratified on ER status.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

The St. Jude valve. Thrombolysis as the first line of therapy for cardiac valve thrombosis.

BACKGROUND: Thrombolytic therapy is a promising alternative to valve replacement in the management of prosthetic valve thrombosis. We sought to determine the short- and long-term results of treating thrombosed St. Jude heart valves with thrombolytic therapy as the primary treatment modality. METHODS AND RESULTS: Between March 1978 and December 1991, 988 patients underwent implantation of St. Jude prosthetic valves at our medical center, and all patients with thrombosed valves were identified prospectively. During this period, 17 patients (13 women; mean age, 66.8 +/- 19.0 years) developed prosthetic valve thrombosis (11 aortic, six mitral). In six patients, Coumadin was stopped in preparation for elective surgery. The clinical presentation was congestive heart failure in 13, syncope and fatigue in two, and a cerebrovascular accident in one; one patient was asymptomatic. The average duration of symptoms was 11.7 +/- 12.0 days (range, 1-45 days). Anticoagulation was subtherapeutic in all but one patient at the time of presentation. Cinefluoroscopy was the primary method used for diagnosis and was also used to follow the response to therapy. Twelve patients were treated medically (10 with thrombolytic therapy and two with heparin), three were treated surgically, and two were diagnosed at autopsy. Of the 12 medically treated patients, 10 had marked improvement in leaflet movement and symptoms within 12 hours. Thus, 10 of 12 patients (83%) had a satisfactory response to medical therapy alone. No medically treated patient died or had a major complication resulting in permanent damage. However, four of the 12 medically treated patients had minor complications, including a transient episode of facial weakness in one patient, hematomas in two, and epistaxis in one. Late rethrombosis recurred in two patients in the medically treated group and was successfully retreated with thrombolytic therapy. At 3 months, all patients were alive and well. CONCLUSIONS: Thrombolytic therapy can be used as the first line of therapy for thrombosed St. Jude valves with a low risk of permanent side effects and excellent chances of success. In most cases, surgery can be reserved for patients who do not respond to thrombolytic therapy.

Adolescent↗
PubMed1993

Adjuvant tamoxifen versus placebo in elderly women with node-positive breast cancer: long-term follow-up and causes of death.

PURPOSE: This study analyzes the long-term results and causes of death in elderly women with node-positive breast cancer who participated in a double-blind adjuvant trial that compared tamoxifen with placebo to determine the benefit of 2 years of treatment. PATIENTS AND METHODS: One hundred eighty-one women 65 to 84 years old were given 20 mg of tamoxifen or placebo daily for 2 years after stratification by estrogen receptor status, tumor size, and degree of lymph node involvement. Approximately 30% of patients were older than 70 years and 20% were older than 75 years. Eighty-five percent were estrogen receptor-positive. Median follow-up was 10 years. RESULTS: Among the 168 eligible patients, there have been 98 recurrences (59 placebo v 39 tamoxifen), with reduced distant and bone-only first sites in patients treated with tamoxifen. Median time to failure was 4.4 years for placebo versus 7.4 years for tamoxifen (log-rank P = .001). A similar number of new nonbreast cancers occurred in each arm (seven placebo v six tamoxifen), but a reduced number of opposite-breast cancers (five placebo v one tamoxifen) was noted. Overall, there were 102 deaths (57 placebo v 45 tamoxifen). Median survivals were 8.0 years with placebo and 8.5 years with tamoxifen (log-rank P = .063); 50% of the tamoxifen patients and 33% of the placebo patients are still alive. Sixty-one percent of the deaths were reported to have been caused by breast cancer recurrence, 4% by other cancers, and 22% by the sequelae of non-cancer-related illness, with equal distributions for cardiovascular and cerebrovascular disease. There was no increase in the number of endometrial or other types of cancer, or thrombotic or orthopedic complications in this older group. CONCLUSION: Tamoxifen currently is the treatment of choice for elderly women with breast cancer. It extends the time to treatment failure by 3 years and reduces the number of recurrences, deaths, distant and bone-only first recurrences, and second breast cancers.

Aged↗
PubMed1993

Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.

PURPOSE: The Eastern Cooperative Oncology Group (ECOG) entered 766 patients onto two prospectively randomized surgical adjuvant clinical trials for lymph node-positive breast cancer (T1-3N1M0). Ninety-five percent (n = 728) of eligible patients have complete information on the prognostic covariables under study (tumor necrosis [TN], tumor size, number of positive lymph nodes, age) and a median follow-up duration of 10.3 years. METHODS: TN was defined as confluent cell death in invasive areas of primary cancers, visible at 4 x objective lens magnification. Cox proportional hazards models were used to estimate presence versus absence of TN effects on clinical outcomes over full cross-stratification of variables, including delivery of chemotherapy versus observation only. Time-varying effects were modeled using spline functions of time, and by fixing proportional hazards models separately in the time periods 0 to 2 and 2+ years. RESULTS: Presence of TN was an independent predictor for time to recurrence (TTR) (P = .007) and for survival (P = .0003) in the overall 10-year follow-up period. Presence of TN was also an independent predictor for TTR and for survival (each P < .0001) in the period 0 to 2 years after diagnosis. Spline function time-modeling calculations showed different hazard ratios in the TN-present (TN+) versus TN-absent (TN-) groups for both TTR and survival (each P < .0001). This difference is changing over time (P = .0001 for TTR, P = .0005 for survival). Once a patient has been disease-free beyond 2 years after diagnosis, presence or absence of TN is irrelevant to future prognosis. CONCLUSION: Confluent TN of any dimension in invasive areas of lymph node-positive breast cancer is an independent predictor for early recurrence and death from the disease.

Breast Neoplasms↗
PubMed1993

Pathogenesis of Cheyne-Stokes respiration in patients with congestive heart failure. Relationship to arterial PCO2.

In order to determine which patients with congestive heart failure (CHF) develop Cheyne-Stokes respiration (CSR) during sleep, we compared the cardiorespiratory profiles of CHF patients with CSR to those of CHF patients without CSR. Overnight polysomnography and continuous transcutaneous PCO2 (tc PCO2) monitoring, estimation of left ventricular ejection fraction (LVEF), pulmonary function tests, and chest radiograph were performed on 16 consecutive patients with chronic, stable CHF. The tc PCO2 monitor (Kontron 7640) was calibrated so that measurements reflected arterial PCO2 values. A mean value was calculated for wakefulness (W) and total sleep time (TST). Circulation time (CT) from the lung to the carotid body was estimated from the end of an apnea or voluntary breath-hold to the nadir of oxygen desaturation recorded on an ear oximeter. The duration of CSR was expressed as a percent of TST. Nine patients developed CSR during sleep (52.5 +/- 31.6 percent TST) (group 1) and 7 did not (group 2). All patients were male and both groups were a similar age (64 +/- 8 vs 63 +/- 4 years) and weight (body mass index, 28.1 +/- 3.5 vs 25.4 +/- 3.4 kg/m2). There were no significant intergroup differences between LVEF (22 +/- 5.2 vs 24.1 +/- 5.2 percent), CT (19.1 +/- 3.6 vs 15.9 +/- 6.7 s), SaO2 (W) (94 +/- 1.2 vs 92.4 +/- 2.1 percent), and SaO2 (TST) (90.8 +/- 2.7 vs 92.4 +/- 2.1 percent). The tc PCO2 (W) was lower in group 1 (34.4 +/- 3.5 vs 38.1 +/- 1.9 mm Hg), increased during sleep by a similar amount in both groups (1.6 +/- 1.5 vs 2.1 +/- 2.2 mm Hg), and was significantly lower during sleep in group 1 (36.1 +/- 3.4 vs 40.2 +/- 2.2 mm Hg). We conclude that CHF patients with CSR hyperventilate during sleep and wakefulness and that CHF patients with awake hypocapnia are more likely to develop CSR during sleep. These findings indicate that arterial PCO2 is important in determining which CHF patients develop CSR.

Blood Gas Monitoring, Transcutaneous↗
PubMed1992

The long-term growth and development of children exposed to Depo-Provera during pregnancy or lactation.

Children exposed to the injectable contraceptive Depo-Provera (DMPA) during pregnancy (N = 1,207), and/or during breastfeeding (N = 1,215) were exposures during pregnancy or breastfeeding. Weights and heights were measured for all children, and information on signs of puberty obtained for children aged ten and over. Cross-sectional weights and heights by age of DMPA-exposed children were similar to those for controls. Children with DMPA exposure during pregnancy and lactation had an increased risk of suboptimal growth in height, defined as less than two Z scores on NCHS standards (RR = 1.4, 95% CI 1.2-1.8). However, after adjustment for socioeconomic factors by multiple logistic regression, there was no increased risk of impaired growth among the DMPA-exposed children (RR = 1.1, 95% CI 0.8 - 1.6). With the exception of a delay in onset of reported pubic hair growth among DMPA-exposed girls, there were no significant effects on attainment of puberty. We conclude that use of DMPA during pregnancy or breastfeeding does not adversely affect the long-term growth and development of children.

Adolescent↗
PubMed1992

Children's drawings of topics differing in emotional significance--effects on placement relative to a self-drawing: a research note.

Children aged 4-6 years were asked to add drawings of someone they liked and someone they disliked to a picture of themselves. Liked figures were drawn closer than disliked figures to the self-figure only when the procedure was standardized and controlled so as to equate the tasks of positioning each of the added figures. With unmatched positioning tasks there was no effect of significance of figure on placement. The data demonstrate that a child's emotional attitude to a figure can affect its placement in a drawing, but that the effect is weak and easily masked.

Art↗
PubMed1992

NMDA-receptor-independent long-term potentiation.

Although NMDA-R-dep LTP in the hippocampus has received much attention, it is clear that many types of LTP do not involve NMDA receptors. While early studies of NMDA-R-indep LTP were done in invertebrates, an NMDA-R-indep LTP is also seen in at least three excitatory pathways of the hippocampus. There would appear to be quite diverse mechanisms of induction of NMDA-R-indep LTP, although in most cases there is evidence, or at least a suggestion, that Ca2+ is involved. At the hippocampal CA3 MF synapse, activation of voltage-gated Ca2+ channels has been proposed as a trigger for LTP induction, and this may also be the case for certain types of LTP at the SC synapse in CA1 (25, 40). The modulation of both MF LTP and Ca2+ channels by beta-adrenoreceptor and muscarinic agonists suggests that specifically the L-type channel is critical for MF LTP induction. L-type Ca2+ channels may also be involved in NMDA-R-indep LTP at SC synapses (6, 40). Clearly more work is needed to test these possibilities. In addition, it will be interesting to discover whether voltage-gated Ca2+ channels play a role in LTP in other areas of the brain such as the cerebral cortex and amygdala (24).

Animals↗
PubMed1992

Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial.

PURPOSE: A randomized trial was performed in premenopausal postoperative women with ipsilateral axillary node-positive (N+) breast carcinoma and known estrogen receptor (ER) status to assess the efficacy of an Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-based induction regimen and 5 or more years of tamoxifen (Tam). PATIENTS AND METHODS: Patients received 12 28-day cycles of cyclophosphamide 100 mg/m2 orally days 1 to 14, methotrexate 40 mg/m2 intravenously (IV) days 1 and 8, fluorouracil 600 mg/m2 IV days 1 and 8, prednisone 40 mg/m2 orally days 1 to 14, and Tam 10 mg orally twice daily (CMFPT), or the same regimen plus halotestin 10 mg orally twice daily (CMFPTH) alternating monthly with 22-day cycles of vinblastine 4.5 mg/m2 IV day 1, Adriamycin 45 mg/m2 IV day 1, thiotepa 12 mg/m2 IV day 1, halotestin, and Tam (ALTER). Prednisone in the ALTER regimen was stopped after the second CMFPTH cycle. After 12 cycles, patients were again randomized to stop or continue Tam. After 5 years, patients on Tam were again randomized to continue or stop Tam; the results from this randomization are still coded. Among 533 analyzed induction cases, 263 received CMFPT and 270 ALTER. Among 396 analyzed maintenance cases, 201 continued Tam and 195 were observed. Pretreatment characteristics were balanced among treatments. The median follow-up times are 5.1 years for induction and 4.1 years for maintenance. RESULTS: The time to relapse (TTR) was superior for the ALTER regimen (P = .04) and for the maintenance Tam (P = .05). Overall survival comparisons between the regimens are not statistically different. A longer TTR was associated with decreasing nodal involvement, ER+ status, and increasing age. The favorable effects of decreasing nodal involvement and ER+ status carried over to survival; a progesterone receptor-positive (PgR+) status and decreasing tumor size were also associated with longer survival. Development of amenorrhea was associated with improved TTR and survival. Toxicity was similar for the two induction regimens and for the two maintenance regimens. Overall relapse patterns were similar among the induction regimens, but continuing Tam led to fewer locoregional relapses. CONCLUSION: The results suggest significant overall TTR therapeutic benefits of an Adriamycin-containing alternating induction regimen and of continuing maintenance Tam therapy for at least 5 years.

Adult↗