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Biomedical subjects

R Seymour

Publications and source records attributed to R Seymour.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of in vivo administration of IL-3 and IL-6, alone and in combination with G-CSF, GM-CSF or IL-1, on haematopoiesis, graft-versus-host disease and survival after murine haematopoietic stem cell transplantation.

We have explored the effect of IL-3 and IL-6, each alone and in combination with G-CSF, GM-CSF or IL-1, on neutrophil and platelet recovery in BALB/c mice (H-2d) given 10 Gy total body irradiation followed by 10(7) bone marrow cells and 10(6) spleen cells from C57BL6 donors (H-2b), as well as the effect of IL-3 alone and IL-6 alone on graft-versus-host disease (GVHD) and survival. Neither IL-3 alone nor IL-6 alone significantly increased the circulating absolute neutrophil count (ANC) at day 6 post transplant when compared with mice given saline injections (ANC 0.31 x 10(9)/l). G-CSF and IL-1, each alone, significantly raised the day-6 ANC (0.58 x 10(9)/l, p = 0.02; 0.67 x 10(9)/l, p = 0.007 respectively). However, IL-3, 200 ng twice daily, significantly increased the day-6 ANC when used in combination with GM-CSF (0.49 x 10(9)/l, p = 0.003) or with IL-6 (0.66 x 10(9)/l, p = 0.004), as well as with G-CSF (0.62 x 10(9)/l, p = 0.007) or with IL-1 (0.49 x 10(9)/l, p = 0.003). Apart from the combination with IL-3, IL-6 significantly raised the day-6 ANC only in combination with G-CSF (0.79 x 10(9)/l, p = 0.007). When used alone, both IL-6 and G-CSF raised the day-6 platelet count (312 x 10(9)/l, p = 0.02 and 309 x 10(9)/l, p = 0.01 respectively) compared with control mice (216 x 19(9)/l). IL-3 alone resulted in a platelet count of 303 x 10(9)/l (p = 0.06). In combination, only IL-3 with G-CSF significantly increased the value over that of saline control mice (328 x 10(9)/l, p = 0.02). IL-3 200 ng alone twice daily and IL-6 200 ng alone twice daily for 14 days post transplant resulted in survival not different from that of mice given saline injections. However, IL-3 500 ng twice daily for 14 days resulted in impaired survival and accelerated weight loss. In summary, while neither IL-3 nor IL-6 (nor GM-CSF) used alone accelerated neutrophil recovery post transplant, the combinations of IL-3 plus IL-6 and IL-3 plus GM-CSF did so. IL-6 (and G-CSF) accelerated platelet recovery post transplant, but combining IL-3 or IL-6 with the other cytokines was generally unsuccessful in this regard. Higher-dosage IL-3 appeared to accelerate graft-versus-host disease and impair survival, thus providing indirect evidence of the involvement of this cytokine in the mediation of GVHD.

Animals↗
PubMed1994

Reduced tamoxifen accumulation is not associated with stimulated growth in tamoxifen resistance.

To study tamoxifen resistance-stimulated growth, 30 female ovariectomized nude mice were implanted with tamoxifen-resistant tumors and treated with 10-1000 micrograms/day of tamoxifen citrate subcutaneously. Tamoxifen stimulated MCF-7 tumor growth in a dose-dependent manner, with tumoral tamoxifen concentrations increasing proportionally to the dose (1-13 nmol/g), as measured by high-performance liquid chromatography (HPLC). Flow-cytometric analysis revealed that tamoxifen-resistant tumors had a different DNA content as compared with wild-type MCF-7 cells. In contrast to earlier results, these data suggest that tamoxifen resistance-stimulated growth is associated with increasing rather than decreasing tumoral tamoxifen concentrations. Furthermore, the observed ploidy changes in the tamoxifen-resistant tumors imply that a genetic basis may exist for the development of tamoxifen resistance.

Animals↗
PubMed1994

Corticosteroid prophylaxis for patients with increased risk of adverse reactions to intravascular contrast agents: a survey of current practice in the UK.

There is no definite experimental evidence that prophylactic corticosteroids reduce the frequency or severity of adverse effects from low-osmolar contrast agents in patients at increased risk of reaction. There is no consensus in terms of how prophylaxis should be conducted. We have studied current radiologists' practice in the UK by sending postal questionnaires to 212 radiologists randomly selected from a list of current consultants who are Fellows of the Royal College of Radiologists. One hundred and seventy (80.2%) of the 212 questionnaires were completed. The majority of radiologists routinely use non-ionic low osmolar contrast media for intravenous administration, only 30 (17.6%) routinely using conventional ionic agents and six (3.5%) ionic low osmolar agents. All 170 use low osmolar contrast media for those patients perceived to be at increased risk of adverse reactions. Seventy-six radiologists (44.7%) never use steroid cover. There is no consistent practice amongst the 94 consultants (55.3%) who do use steroid cover. The indications for prophylaxis vary, as do the corticosteroid used and the dose regime employed. The total dose used varied from the equivalent of 7.5 mg to 400 mg of prednisolone, and the duration of prophylaxis varied from a single dose to a 4 day course. One hundred and forty-two radiologists (83.5%) would welcome nationally agreed guidelines for the use of steroid cover. The great variation in the use of steroid cover in the UK reflects the lack of clear evidence of its benefit in combination with low osmolar contrast media.

Adrenal Cortex Hormones↗
PubMed1993

Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix.

PURPOSE: Prospective, single arm, Phase I/II trial performed to assess the efficacy and toxicity of the concomitant use of weekly cisplatin and pelvic radiotherapy in patients with locally advanced carcinoma of the cervix. METHODS AND MATERIALS: Between December 1988 and April 1991, 50 previously untreated patients with bulky, locally advanced, squamous cell carcinoma entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pre-treatment staging procedures. The International Federation of Gynecology and Obstetrics stage distribution was as follows: IIA three patients, IIB seventeen, IIIA two, IIIB 25, and IVA three. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose rate intracavitary treatments given on a weekly basis to a total dose of 30 Gy to point A. Cisplatin 30 mg/m2 was also given weekly starting on day 1 of radiotherapy. RESULTS: With a median follow-up time of 27 months, complete response was seen in 88% (44/50) of the patients. The actuarial survival rate at 44 months was 65%. Total pelvic failure rate was 26% (13/50). Of the 44 patients who achieved a complete remission, only seven have failed in the pelvis. Distant disease was observed in 24% of the cases. Treatments were well tolerated with no patient requiring an interruption in the radiotherapy. However, the incidence of late gastrointestinal toxicity was high, with 10 patients developing a rectal ulcer (four colostomies for severe bleeding), two patients a small bowel obstruction, and two patients a recto-vaginal fistula. Moreover, gastrointestinal complications appeared sooner than expected, at a median follow-up time of 11 months after completion of treatment. CONCLUSION: The combination of weekly cisplatin and radiotherapy appears to be a very effective regimen for patients with locally advanced carcinoma of the cervix, but resulted in a relatively high frequency of late gastrointestinal complications.

Adult↗
PubMed1993

Tamoxifen stimulates in vivo growth of drug-resistant estrogen receptor-negative breast cancer.

An estrogen receptor-negative, multidrug-resistant MDA-MB-A1 human breast cancer cell line was grown in culture with and without a noninhibitory concentration (0.5 microM) of tamoxifen for 122 days. Tamoxifen-treated and control cells were inoculated into opposite flanks of nine nude mice, where they produced measurable tumors in every case. Six of the animals were treated with tamoxifen at 500 micrograms/day for 22 days. Although no inhibitory nor stimulatory effect of tamoxifen was seen in vitro, tamoxifen had a clear tumor-growth-stimulating effect in mice. The most pronounced stimulatory effects were observed in the cells that had been cultured with tamoxifen. Within 3 weeks of the start of tamoxifen therapy, the cells grown in the presence of tamoxifen produced tumors with a mean size of 380 mm2, whereas the cells not pretreated with tamoxifen had tumors of 220 mm2. In contrast, in mice not receiving tamoxifen, the sizes of the tumors were 190 and 140 mm2, respectively. These preliminary results suggest that prolonged in vitro tamoxifen exposure induces cellular changes that result in tumors that are stimulated to grow faster in mice following tamoxifen treatment.

Animals↗
PubMed1992

The effect of hemiplegia on blood pressure measurement in the elderly.

The blood pressure in both arms of 103 unselected hemiplegic patients was measured using a random-zero sphygmomanometer. Although for the whole sample the mean blood pressure in the paretic and unaffected arm was similar, a significant difference was found when the patients were subdivided according to the tone of the arm. The blood pressure was higher in paretic arms of patients with a spastic stroke and lower in the affected arm if the tone was flaccid. No other characteristics were associated with significant blood pressure differences, so that the findings appear to be directly related to changes in muscle tone. After a stroke the blood pressure should always be measured in the unaffected arm because changes in tone make measurements unreliable.

Aged↗
PubMed1992

Cytokine activity after allogeneic bone marrow transplantation. IV. Production of mRNA for IL-3 and GM-CSF by mitogen-stimulated circulating mononuclear cells.

The ability of circulating mononuclear cells from recipients of HLA identical sibling marrow transplants to generate messenger (m) RNA for the haemopoietic growth factors interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upon mitogen stimulation was investigated. The amount of IL-3 mRNA per ml of blood and IL-3 mRNA per 10(7) mononuclear cells as well as the amount of GM-CSF mRNA per ml of blood was significantly lower in transplant recipients than in normal volunteers. Lower values for mRNA expression for both IL-3 and GM-CSF were associated with the use of immunosuppressive therapy post transplant. No correlation was found between the expression of message for either cytokine, or the presence or absence of acute graft-versus-host disease at the time of testing. While there was no correlation between the quantity of GM-CSF message produced and time elapsed post transplant, IL-3 message expression increased slightly with increasing time post transplant. These defects of haemopoietic regulators constitute another parameter of impaired cellular immunity occurring after allogeneic marrow transplantation.

Bone Marrow Transplantation↗
PubMed1991

In vivo administration of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF, interleukin-1 (IL-1), and IL-4, alone and in combination, after allogeneic murine hematopoietic stem cell transplantation.

BALB/c mice (H-2d) given 10 Gy total body irradiation (TBI) followed by 10(7) bone marrow (BM) and 10(6) spleen cells from C57BL/6 (H-2b) donor mice received recombinant cytokines intraperitoneally (IP) twice daily. The effect on neutrophil recovery rate, graft-v-host disease (GVHD), and survival was assessed. Four reagents were used: granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-1 (IL-1) and IL-4, both alone and in combination. The most effective combination for increasing the circulating absolute neutrophil account (ANC) above the control value at day 7 posttransplant was the combination of G-CSF and IL-1 (mean ANC 2.4 +/- 1.6 x 10(9)/L as compared with control value of 0.07 +/- 0.05, P less than .02), followed by G-CSF alone (mean ANC 1.1 +/- 0.2, P less than .0001), the combination of GM-CSF plus IL-1 (mean ANC 0.8 +/- 0.3, P less than .002), and the combination of G-CSF plus GM-CSF (mean ANC 0.8 +/- 0.3, p less than .005). At day 10 posttransplant, the most effective combination in raising the ANC was the combination of G-CSF plus GM-CSF (mean ANC 7.5 +/- 2.3 as compared with control value of 3.5 +/- 1.1, P less than .01), followed by G-CSF alone (mean ANC 6.9 +/- 2.1, P less than .02). At the doses used, neither G-CSF nor GM-CSF had a deleterious effect on the incidence or severity of GVHD; indeed, GM-CSF was associated with improved survival. In contrast, IL-1 at doses greater than or equal to 100 ng twice daily caused marked early mortality, and there was a suggestion that IL-4 at doses of 500 ng twice daily resulted in increased late mortality, possibly owing to exacerbation of GVHD. This model appears to be of value for exploring the use of hematopoietic growth factors before they are used clinically in marrow allograft recipients.

Animals↗
PubMed1991

Is post-operative intracavitary therapy a necessary component of treatment for carcinoma of the endometrium?

The role of intracavitary therapy in combination with external pelvic radiotherapy for endometrial carcinoma remains controversial. To determine the pelvic failure rat in patients receiving only external pelvic radiotherapy following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) for carcinoma of the endometrium, we undertook a retrospective review of all patients referred to the Radiation Oncology Department from January 1977 through December 1984. Patients with grade I, superficially invading tumors were excluded from this analysis. 52 patients were eligible for the study. Three patients who were lost to follow-up immediately after completion of external beam irradiation were excluded, leaving a total of 49 evaluable patients. The median follow-up time is 61 months. Pelvic failure was seen in only 2 patients (4%), both of them occurring concurrent with distant disease. No vaginal vault failures were observed. Overall actuarial survival at 5 years was 82%. We conclude that external beam pelvic radiotherapy alone without intracavitary boost appears to be an adequate treatment for patients undergoing TAHBSO for carcinoma of the endometrium.

Adenocarcinoma↗
PubMed1991

Unusually severe traumatic uveitis associated with occult ankylosing spondylitis.

We describe two young men in whom severe anterior uveitis developed following relatively minor corneal trauma. Investigation revealed ankylosing spondylitis in both cases; neither had previously experienced uveitis. We are unaware of any previous reports implicating minor ocular trauma in precipitating a first episode of uveitis associated with ankylosing spondylitis. The possibility of occult ankylosing spondylitis should be considered in cases of disproportionately large anterior chamber reactions to minor ocular trauma.

Adult↗
PubMed1990

Sertraline in obsessive-compulsive disorder: a double-blind comparison with placebo.

Many agents that affect the brain's serotonergic system appear to be at least partially effective in the treatment of patients with obsessive-compulsive disorder. However, in this 10-week double-blind trial in which 10 patients received sertraline and nine received placebo, sertraline was ineffective according to four measures of obsessive-compulsive symptoms. The authors discuss the implications of these preliminary findings for the serotonergic theory of obsessive-compulsive disorder and the need to explore the role of other neurochemical systems in this disorder.

1-Naphthylamine↗
PubMed1990

A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory.

Thirty-eight patients with primary obsessive-compulsive disorder participated in a 10-week, double-blind, placebo-controlled trial of the potent, selective serotonin reuptake inhibitor fluvoxamine. Fluvoxamine was significantly better than placebo on two of three measures of improvement in obsessive-compulsive symptoms. The authors also compared studies of the serotonergic agents fluvoxamine, sertraline, fluoxetine, and clomipramine and found that a greater effect size was associated with less serotonergic specificity and that some ability to affect other neurotransmitter systems may be a necessary but not sufficient requirement for antiobsessional activity. These data lend only partial support to a serotonin hypothesis of obsessive-compulsive disorder.

1-Naphthylamine↗