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Biomedical subjects

J R Williams

Publications and source records attributed to J R Williams.

At least 19 recordsLinked to original sources
PubMed1992

Oxytocin and social bonding.

The prairie vole is an excellent model for examining the neurobiology of social attachment, and in particular of pair-bond formation. In female prairie voles either sexual interactions or oxytocin infusions can hasten the formation of a partner preference. These results implicate oxytocin in the formation of adult heterosexual social bonds. In conjunction with work on other social systems described in this volume, these findings also support the suggestions of Klopfer and Newton that oxytocin may be important in coordinating mammalian social interactions with other critical reproductive events such as birth, lactation, and sexual behavior.

Aggression↗
PubMed1992

Partner preference development in female prairie voles is facilitated by mating or the central infusion of oxytocin.

Results of these experiments indicate that females given at least 24 hours of cohabitation with a male develop a social preference for the familiar partner versus a stranger. Mating is not essential for the development of partner preferences, but clearly facilitates the onset of preferences. Females given six hours of cohabitation showed partner preferences only if they mated with the partner during cohabitation (Experiment 2) or if they received oxytocin (Experiment 3). Females that continued to mate during preference tests (Experiment 2, n = 4) mated exclusively with the partner. Oxytocin infusions, even in the absence of mating or estrogen priming, facilitated the development of partner preferences.

Animals↗
PubMed1992

Prehospital thrombolysis in a rural community: short- and long-term survival.

In order to assess the feasibility and outcome of using prehospital thrombolysis in acute myocardial infarction in a rural community, we performed an open randomized study of patients with symptoms of acute myocardial infarction of less than 6 hours. One hundred and forty-five patients with acute myocardial infarction were allocated to receive IV streptokinase prehospital by means of a mobile coronary care unit (MCCU) (n = 43) or to receive IV streptokinase in hospital (n = 102). The mean delay time to treatment was 138 minutes (MCCU group) and 172 minutes (hospital group) (p less than 0.02). Reperfusion time was 88 minutes for the MCCU group and 92 minutes for the hospital group. Mortality at 14 days was 2.3% for the MCCU group and 11.7% for the hospital group (p less than 0.05). Six month mortality was 4.9% for the MCCU group and 17.3% for the hospital group (p = 0.03). Mortality at 1 year was 6.1% for the MCCU group and 20.0% for the hospital group (p = 0.04). There were no significant adverse events in either treatment group. Thus, prehospital thrombolysis by streptokinase is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in both short- and long-term survival with no apparent reduction in safety profile.

Adult↗
PubMed1992

Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience.

Prairie voles (Microtus ochrogaster) exhibit a monogamous mating system characterized by long-term pair bonds between mates. The purpose of this study was to examine the effect of cohabitation time and sexual experience on the development of pair bond formation in female prairie voles. Females that were allowed to cohabit for 24 hr or more, with or without mating, exhibited a strong social preference for a familiar partner versus a strange male. Females that cohabited and mated for 6 hr showed strong preferences for a familiar partner, while cohabitation for less than 24 hr, without mating, did not result in preferences for the familiar male. These results indicate that mating was not essential for partner preference formation; however, preferences developed more rapidly when mating occurred.

Aggression↗
PubMed1992

Olfactory bulb removal affects partner preference development and estrus induction in female prairie voles.

In female prairie voles (Microtus ochrogaster) bilateral olfactory bulbectomy reduced affiliative behavior, as measured by social contact, and prevented the formation of partner preferences. Unilateral olfactory bulb removal did not significantly influence affiliative behavior, but did inhibit partner preferences. Bilateral, but not unilateral, bulbectomy significantly reduced the proportion of females exhibiting behavioral estrus following male exposure. In contrast to affiliative and sexual behavior, parental behavior was not significantly affected by either bilateral or unilateral olfactory bulbectomy. These results suggest that divergent sensory-neural pathways underlie social, sexual, and parental behaviors in this species.

Aggression↗
PubMed1992

Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

Calcitriol↗
PubMed1992

Sensitization processes in human tumor cells during protracted irradiation: possible exploitation in the clinic.

Recent studies documenting the response of several human tumor cell lines to protracted, continuous irradiation and to acutely delivered radiation, suggest that tumor control may be enhanced with a tumor therapy combining external beam fractionated therapy and protracted irradiation from radiolabeled antibodies. We have evaluated the cytotoxic effect of continuous, protracted irradiation (0.005 Gy/hr to 0.50 Gy/hr) and acutely delivered high-dose-rate irradiation (1.0 Gy/min) on monolayer cultures of human tumor cell lines. Colony formation in these studies was analyzed by the seven-parameter simulation model of Dillehay. Additionally, for some cell lines, cultures were challenged during irradiation with an acute dose of 2.5, 5.0, 7.5 or 10.0 Gy at high-dose-rate. Results from these various studies indicate an altered cellular radiosensitivity occurs for some cell lines during protracted irradiation. At least two mechanisms have been identified that underlie this altered radiosensitivity. One mechanism, G2B, associated with redistribution within the cell cycle, has been previously described by Mitchell and others, and is associated with the phenomenon termed "the inverse dose-rate effect". The other mechanism is only observable following a challenge by acute high-dose-rate irradiation. We have termed this phenomenon "protracted-exposure-sensitization." The characteristics of these two mechanisms are discussed from the perspective of clinical therapeutic exploitation of combined external beam fractionated therapy and radiolabeled immunoglobulin therapy.

Cell Cycle↗
PubMed1992

Selection of reagents for human radioimmunotherapy.

Promising response rates are noted in patients with refractory Hodgkin's disease after radioimmunoglobulin therapy (RIT) with Yttrium-90 labeled polyclonal antiferritin. To explore the most efficacious selection of RIT reagents for use in humans, experimental animal data are reviewed for radiolabeled antiferritin and B72.3. Nude mice with subcutaneously implanted human malignancies provide an excellent primary screen for radiolabeled antibodies under consideration for use in humans. They provide information on the potential of a new reagent to target a human malignancy in vivo. The other determinant of the therapeutic ratio of RIT reagents--normal tissue toxicity--is best analyzed in large animals, such as dogs. Hematologic toxicity is dose limiting in all species and best predicted by a prescription of radiolabeled antibodies in mCi per kilogram body weight and the presence or absence of bone marrow targeting. Per cGy, RIT is more effective in causing BM damage in dogs than in rats. In dogs, bone marrow transplantation with autologous cryopreserved bone marrow cells or G-CSF treatment can accelerate hemopoietic recovery and granulopoiesis, respectively, after RIT. When dose escalation beyond bone marrow toxicity is performed, the liver (dog) or the intestinal tract (rat) become the next dose limiting tissue in dose escalation studies. Significant improvement in RIT results will be achieved when the normal liver uptake of chelated monoclonal antibody in dogs and in human patients can be prevented. The described animal models and continued investigations of RIT in patients with endstage Hodgkin's disease will allow for further improvement in the therapeutic ratio of RIT and the applicability of RIT in humans.

Animals↗
PubMed1992

The influence of the site of sampling and assay medium upon the measurement and interpretation of blood lactate responses to exercise.

UNLABELLED: This paper reports the findings of two investigations into methodological problems associated with the interpretation of blood lactate (BLa) in the sports sciences. In Experiment 1, brachial artery (A), antecubital venous (V) and fingertip capillary (C) blood samples were drawn simultaneously from nine subjects (mean age 21.1 +/- 1.3 years) during an incremental treadmill protocol and immediately assayed for BLa concentration. Experiment 2 investigated the extent of lactate concentration differences in whole blood (WB), lysed blood (LB) and plasma (P) measured using a YSI 23 AM analyser. In Experiment 1, a comparison of the mean BLa concentrations obtained from the three sites revealed no significant differences (P greater than 0.05). Correlations between BLa samples from different sites were very high, with r values ranging from 0.858 to 0.983. In Experiment 2, the mean lactate concentrations were: WB, 4.7 +/- 2.7 mM; LB, 5.0 +/- 3.0 mM; P, 7.0 +/- 3.8 mM. Plasma (P) values were significantly higher than WB and LB. Values from all sites were highly correlated with coefficients ranging from 0.963 to 0.987. IN CONCLUSION: (1) Significant arterial and venous BLa concentration differences do not exist during incremental treadmill exercise. (2) As capillary BLa concentrations reflect arterial values, their use in laboratory and field settings is recommended. (3) Lactate concentration differences in whole blood, lysed blood and plasma will influence the assessment of performance at fixed lactate reference values. (4) If the inter-laboratory test procedures are to be standardized and results compared, precise reporting of lactate sampling and assay techniques is critical.

Adult↗
PubMed1992

A dosimetric intercomparison of megavoltage photon beams in UK radiotherapy centres.

A dosimetry intercomparison has been carried out for all 64 radiotherapy centres in the UK. Doses were measured with an ionization chamber in an epoxy resin water-substitute phantom of relatively simple geometry. Reference-point measurements were made for all MV photon beams. For 61 Co-60 beams, a mean ratio of measured-to-stated dose of 1.002 was observed with a standard deviation of 0.014, whilst for 100 MV x-ray beams, the corresponding figures were 1.003 and 0.015. 97% of beams lay within a +/- 3% deviation. One measurement was instrumental in discovering a large discrepancy. Doses were also investigated in two planned three-field distributions at one beam quality in each centre. One of these was in a homogeneous phantom, whilst the second included a lung-equivalent insert. Doses were measured at the central point and at four other points in the high dose volume. In both situations, the mean ratio of measured-to-calculated doses for all points was 1.008, with standard deviations of 0.027 and 0.035 for the uniform and non-uniform phantoms, respectively. Discrepancies over 5% were followed up. The work must be viewed in the context of other international intercomparisons and is an essential part of wider radiotherapy audit processes.

Humans↗
PubMed1992

Influence of radiologist grade on fluoroscopic patient dose.

The effect of radiologist grade on patient dose during fluoroscopic barium studies was assessed over a one-year period in a large teaching hospital using area-kerma measurements made with a Diamentor M2 system. The number of studies investigated was 164 for barium swallows, 274 for barium meals and 1288 for barium enemas. The patient's AP thickness was assessed at the abdominal level from a formula combining the patient's estimated height and weight. For each study there was no significant change in AP thickness as a function of radiologist grade. For all barium studies there was a trend for both the screening time and the patient dose to fall to a minimum for the grades third-year registrar/first-year senior registrar. From this group to consultant level the dose and screening time rose.

Fluoroscopy↗
PubMed1991

A system for the quality audit of treatment dose delivery in radiotherapy.

Treatment planning is a process requiring the cooperation of a number of different staff groups. The possibility for error is well recognised and quality control procedures are necessary to ensure that the chances of errors in planning leading to incorrect treatments are as low as possible. An audit system is described which is based on the calculation of the dose delivered to the patient using the parameters set for treatment as input data. The calculated dose is compared with the prescribed dose and errors greater than a defined limit are flagged. During a period of 19 months during which this audit procedure has been operating a total of 14 errors in excess of 5% were discovered and corrected, this is approximately 0.5% of the total number of plans checked.

Humans↗
PubMed1991

A method for quantitative autoradiography over stained sections of tumors exposed in vivo to radiolabeled antibodies.

Quantitative autoradiography can be an important element in calculating dose patterns delivered to tumors and normal tissues of animals injected with radiolabeled antibodies. In this article we develop a computer algorithm that permits quantitative evaluation of grain density over large areas of stained tissue with minimal grain counting. This algorithm, using spectral classification of brightfield and darkfield images, image ratios, and manual counting of small sections of an autoradiograph, yields images defined in terms of grain density, independent of staining artifacts. These quantitative images give a precise indication of intratumor radioimmunoglobulin targeting, and can serve as source functions for dosimetric calculations.

Algorithms↗
PubMed1991

Do not catheterise your nephrectomies.

A retrospective study of 100 consecutive nephrectomy patients showed a 20% catheterisation rate. Of the 11 carried out post-operatively only 4 were for urinary retention. The post-operative catheterisation rate for males was 7.1% and for females 2%. The rate of post-operative retention was 4.4%, which is much lower than that reported from other units. This rate of post-operative catheterisation for retention is so low that in spite of the very mild increase in complications compared with intra-operative catheterisation, the practice of routine prophylactic catheterisation of nephrectomy patients is unnecessary and cannot be recommended.

Adolescent↗