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Biomedical subjects

R Gray

Publications and source records attributed to R Gray.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Preoperative radiological evaluation of the liver by computerized tomographic portography in patients with hepatic tumors.

The main objective of preoperative imaging studies is to define as accurately as possible the number, size, location, and relationship of tumor masses in the liver to pertinent portal and hepatic venous vasculature. Computerized tomographic portography images hepatic veins and segmental portal vein branches and identifies the anatomical location of tumor nodules with excellent sensitivity and a low false-positive rate. The intraoperative correlation of computerized tomographic portography on 30 patients in the last 20 months at this institution shows a sensitivity of 88 per cent with a low rate of false-positivity. The ability to detect metastatic lesions in the liver by computerized tomographic portography diminishes when the lesions are noted to be less than 1 cm. The authors conclude that the preoperative interpretation of the computerized tomographic portogram provides valuable information not previously available to the surgeon operating on the liver.

Adult↗
PubMed1992

Visceral infarction caused by cocaine abuse: a case report.

Cocaine abuse is now known to result in a wide variety of medical illnesses. We report our experience with one patient who had abdominal pain and was found to have near-total infarction of all abdominal viscera. The cause of this and other medical complications of cocaine abuse (i.e., extreme vasoconstriction) is discussed in detail. Physicians should maintain a high index of suspicion when dealing with complaints of abdominal pain by cocaine users.

Adult↗
PubMed1992

Lactate measured in diluted and undiluted whole blood and plasma: comparison of methods and effect of hematocrit.

We evaluated a new analyzer that measures lactate in undiluted whole blood by direct (or undiluted) amperometry [Nova Stat Profile 7 Analyzer (SP7); Nova Biomedical, Waltham, MA] by comparing it with two other analyzers, one for measuring lactate in whole blood by indirect (or diluted) amperometry [Model 2300; Yellow Springs Instrument Co. (YSI), Yellow Springs, OH] and another for measuring lactate in plasma by enzymatic colorimetry (aca; Du Pont Co., Wilmington, DE). All between-method comparisons of the three methods showed that the results for plasma were comparable (Sy/x = 0.24-0.33 mmol/L). Within-method comparisons by the YSI differed substantially between plasma and whole blood (Sy/x = 0.48 mmol/L), but within-method comparisons by the SP7 produced better agreement between plasma and whole blood (Sy/x = 0.18 mmol/L). The difference between whole blood and plasma by YSI is related to hematocrit, with the greatest differences noted for samples with the highest hematocrit. Serum lactate measured by SP7 had between-day imprecision (CV) ranging from 12% at 0.5 mmol/L to 4.2% at 3.7 mmol/L, showed a linear standard curve to at least 11.5 mmol/L, and was independent of hematocrit. There was a mean bias of approximately 0.4 mmol/L for results in the reference range for both plasma and whole blood by SP7 compared with plasma results by either aca or YSI.

Autoanalysis↗
PubMed1992

Intensive chemotherapy with or without additional bone marrow transplantation in paediatric AML: progress report on the MRC AML 10 trial. Medical Research Council Working Party on Childhood Leukaemia.

The Medical Research Council's AML 10 Children Trial commenced in 1988. It is a multicentre collaborative study based on 4 courses of intensive chemotherapy with additional allogeneic bone marrow transplantation for children with a matched sibling donor. The remaining children are randomised either to an autologous transplant using unpurged marrow or stopping therapy. To date 156 eligible patients have been entered with a CR rate of 91%. 56% of children are still alive 2 years after trial entry and 57% are in CR 3 years after achieving CR. The treatment regimen is intensive but mortality and morbidity are acceptable. The study will need to accrue patients for a further 2 to 3 years in the hope of defining the role of allogeneic and autologous marrow transplantation.

Acute Disease↗
PubMed1992

Prognostic potential of DNA flow cytometry measurements in node-negative breast cancer patients: preliminary analysis of an intergroup study (INT 0076).

An ancillary study (INT 0076) to the Intergroup clinical trial of node-negative breast cancer patients (INT 0011) was performed to retrospectively evaluate DNA flow cytometry measurements of ploidy (DNA content) and proliferative capacity (S-phase fraction) for their ability to predict time to recurrence. Of the 915 patients eligible for the clinical trial, 788 were registered for the ancillary flow cytometry study (INT 0076). Four hundred and three of these patients [estrogen receptor (ER)-positive, tumor size less than 3 cm] had been registered to the observation arm of the clinical trial and 385 (ER-negative and/or tumor size greater than or equal to 3 cm) had been randomly assigned to adjuvant chemotherapy (cyclophosphamide, methotrexate, fluorouracil, and prednisone for six cycles) or to observation. Paraffin blocks from 95% (748 of 788) of these patients were obtained, 712 of which had sufficient cancer tissue to be evaluable for the flow cytometric assay. DNA ploidy status (DNA diploid vs DNA aneuploid) was evaluable for 565 (79%) specimens, 64% of which were aneuploid. Proliferative capacity was estimated by the percentage of cells having an S-phase DNA content, using a trapezoidal modeling algorithm(s) as previously described. The median S-phase value for the entire group (both registered and randomly assigned patients) was 6.97%, which defined the cutoff for interpretation of high or low S-phase values. With a median follow-up time of 4.55 years, S-phase fraction, but not ploidy status, is a significant predictor for time to recurrence in both the randomly assigned and the untreated population (observed registered group and observed randomly assigned group).(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1991

Effects on 4080 rats of chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine: a detailed dose-response study.

Four thousand eighty inbred rats were maintained from weaning on various different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA). The principal aim was to characterize the dose-response relationship for the effects of these agents on esophageal cancer (NDEA) or on various types of liver cancer (NDEA and NDMA), although NDEA also caused a few tumors of the nasopharynx and NDMA also caused a few tumors of the lung. The numbers of tumors of mesenchymal and Kupffer cells in the liver were too few to allow easy characterization of the dose-response relationships, and although NDMA induced large numbers of bile duct neoplasms, NDEA did not. Thus, the four principal dose-response relationships studied were of NDEA on esophageal or liver cells and of NDMA on bile duct or liver cells. At doses sufficiently high for the median time to death from the disease of interest to be estimated, relationships were observed of the general form (Dose rate) x (median)n = constant where n was about 2.3 for the first three relationships and about 1 for the last one (NDMA on liver cell tumors). By contrast, at doses sufficiently low for longevity to be nearly normal (median survival about 2.5 years), there remained no material dependence on the dose rate of the age distribution of the induced neoplasms. At these low dose rates, the number of liver (but not of esophageal) neoplasms induced by treatment was simply proportional to the dose rate. This finding is not surprising, since the background incidence of liver (but not of esophageal) neoplasms was appreciable. The linear relationship observed at low dose rates (below 1 ppm) suggests that under these experimental conditions, among rats allowed to liver their natural life span, a dose of 1 ppm of NDEA or NDMA in the drinking water will cause about 25% to develop a liver neoplasm, a dose of 0.1 ppm will cause about 2.5% to do so, and a dose of 0.01 ppm will cause about 0.25% to do so, etc., with no indication of any "threshold." (At these low dose rates, the incidence of liver neoplasms appears likely to exceed greatly that of esophageal neoplasms.) In addition, even quite low dose rates of the test agents caused a variety of nonneoplastic liver abnormalities (e.g., hyperplastic nodules, or shrinkage of hepatocytes) at a frequency roughly proportional to the dose rate.

Animals↗
PubMed1991

Dose and time relationships for tumor induction in the liver and esophagus of 4080 inbred rats by chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine.

A Weibull analysis is presented of the dose and time relationships for the effects on 4080 inbred rats of chronic ingestion in the drinking water of 16 different doses of N-nitrosodimethylamine (NDMA) or N-nitrosodiethylamine (NDEA). The sites chiefly affected were the liver (by both agents) and the esophagus (by NDEA only). Since the experiment continued on into extreme old age, effects became measurable at doses of only 0.01 to 0.02 mg/kg/day, which is an order of magnitude lower than previously achieved. (After only 2 years of treatment, however, the TD50 doses needed to halve the proportion of tumorless survivors would have been about 0.06 mg/kg/day of NDEA, or about 0.12 mg/kg/day of NDMA.) The general pattern of response was that the natural logarithm of the probability of remaining tumorless was given by the product of two terms, the first (the "Weibull b value") depending on the dose rate but not on the duration of exposure and the second depending not on dose at all but only on duration. For all types of tumor the dependence on duration was fairly similar (and for each the second term was taken to be -t7, where t = years of treatment), but for different types of tumor the dependence on dose rate was quite different. For esophageal tumors, the "Weibull b value" was approximately proportional to the cube of the dose rate of NDEA (males 21 d3, females 11 d3, where d = dose rate in mg/kg adult body weight/day), and the background incidence was unmeasurably low. For liver tumors induced by NDEA, the b value was approximately proportional to the fourth power of dose rate + 0.04 mg/kg/day [males, 19 (d + 0.04)4; females, 32 (d + 0.04)4], although the relationships were somewhat different for the different cell types of liver tumor. This one formula implies both approximate linearity at low doses and an approximately cubic relationship within the higher range of doses that was studied. For liver tumors induced by NDMA, the Weibull b value was approximately proportional to the sixth power of dose rate + 0.1 mg/kg/day [males, 37 (d + 0.1)6; females, 51 (d + 0.1)6], again with some variation between liver cell types, and again implying approximate linearity at low doses. These algebraic formulae should, of course, be trusted only in the range of doses where they were derived, and particularly not above it.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1991

Chronic nitrosamine ingestion in 1040 rodents: the effect of the choice of nitrosamine, the species studied, and the age of starting exposure.

In parallel with a larger experiment on 4080 rats fed 16 different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA) from 6 weeks of age, a variety of smaller experiments on a total of 1040 rodents were undertaken and are the subject of the present report. Three separate subjects were addressed. Studies of 16 different concentrations of N-nitrosopyrrolidine and N-nitrosopiperidine given from age 6 weeks onwards to small groups of rats yielded dose-response relationships for the effects of N-nitrosopyrrolidine on liver tumors and for those of N-nitrosopiperidine on tumors of the liver and upper gastrointestinal tract that resembled those seen for NDMA and NDEA, respectively, except that N-nitrosopyrrolidine and N-nitrosopiperidine were less potent [the respective dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment being approximately 0.4 (males) and 0.6 (females) mg/kg adult body weight/day for each agent]. Alternatively, it was estimated that the risks to rats from lifelong exposure to 1 microgram/kg adult body weight/day of each agent might be about 0.1%, and that the risks to rats from lower doses would be proportionately less. Studies of 16 different concentrations of NDEA on small groups of female mice and female hamsters yielded the types of dose response that would be expected for upper gastrointestinal tumors, liver cell tumors, and Kupffer cell tumors in mice (no other types of liver tumor being produced, in contrast with previous reports) and for tracheal and liver cell tumors in hamsters (no clear effect on upper gastrointestinal tumors being apparent in hamsters). The dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment were approximately 0.3 mg/kg adult body weight/day, i.e., 5 times that for the same agent in rats. In part, however, this may be because treatment started at an older age in these species. Studies were undertaken of the effects on esophageal and liver tumorigenesis of starting the treatment of rats with NDEA at 3 or at 20 weeks of age instead of at 6 weeks of age (as in the main experiment). Earlier treatment resulted in slightly greater dosage rates, if dosage was measured in mg/kg/day, and hence in a correspondingly more rapid yield of esophageal tumors, but the effect was not large. By contrast, an earlier start to treatment resulted, after a fixed duration of treatment, in animals having a 3-fold higher incidence rate of liver tumors, while a later start resulted in a 2-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗