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Biomedical subjects

R Fleming

Publications and source records attributed to R Fleming.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cancer chemotherapy in older adults. A tolerability perspective.

The incidence of cancer increases with age. Since the geriatric population is growing, we will be confronted with an increasing number of patients with cancer who are > 65 years of age. The purpose of this review is to address the use of cancer chemotherapy in older persons with respect to its tolerability. We performed a review of the literature using 'Medline' and the bibliographies of pertinent publications. Information about cancer treatment in older adults was extracted with particular attention to chemotherapy-related toxicity in patients aged > 65 years. Comorbid disease, polypharmacy/drug interactions, psychosocial issues and age-related physiological changes are major issues in caring for older patients with cancer. Since older individuals may have a greater number of comorbid illnesses, treatment should be initiated on the basis of physiological rather than chronological age. Comparative studies show that chemotherapy-related toxicity is similar in older and younger patients, with the exception of haematological toxicity, which may be more severe in older patients, and cardiotoxicity, which is more frequent in the elderly. Other evidence suggests that gastrointestinal and neurotoxicities may also be more severe in older individuals. The dosages of chemotherapeutic agents that are primarily renally excreted may require adjustment in older patients. Haematological reserve is decrease in older individuals, and drugs that cause myelosuppression must be used with care. The use of haemopoietic growth factors in geriatric patients is currently being investigated.

Aged↗
PubMed1997

[Analysis of blood utilization in programmed surgery].

The purpose of this study is to analyse the crossmatched blood units for elective surgery and the real amount of transfused blood, the crossmatch:transfusion rate (C:T) which must be less than 2.5. As in other Blood Banks, the differences are more evident in the situations in which the need for blood is very small, the so called "Type and Screen".

Blood Grouping and Crossmatching↗
PubMed1996

Purified urinary follicle stimulating hormone induces different hormone profiles compared with menotrophins, dependent upon the route of administration and endogenous luteinizing hormone activity.

The effects of treatment of patients with gonadotrophin-releasing hormone analogue (GnRHa) combined with purified follicle stimulating hormone (FSH) for in-vitro fertilization (IVF) were investigated in detail to determine the influences of different administration routes and the degree of suppression of luteinizing hormone (LH). Responses to exogenous gonadotrophins were studied in infertile women (n = 60) with normal menstrual rhythm whose endogenous gonadotrophin activity was suppressed using a GnRHa in a long protocol. They were randomized to receive i.m. administration of human menopausal gonadotrophins (HMGim, Pergonal) or purified follicle stimulating hormone (FSH, Metrodin High Purity) administered either i.m. (MHPim) or s.c. (MHPsc). Responses were assessed by measuring plasma FSH, LH, oestradiol, testosterone and progesterone. After stimulation day 4, the MHPsc group showed significantly higher circulating concentrations of FSH than either the MHPim or HMGim group. However, the HMG group showed significantly higher oestradiol concentrations after stimulation day 5 than either MHP group. The differences in circulating oestradiol concentrations in the MHP-treated patients appeared to be strongly influenced by the mean circulating concentrations of LH in the follicular phase. The patients who showed mean follicular phase LH concentrations of < 1 IU/l showed longer follicular phases, lower circulating oestradiol and testosterone concentrations and also lower follicular fluid concentrations of oestradiol and testosterone, indicating a reduction in the normal follicular metabolism of progesterone to androgens and oestrogens under these conditions. This group of patients also showed longer follicular phases, which may have consequences for future clinical management.

Adult↗
PubMed1996

The effect of sperm-mucus interaction test on the outcome of in vitro fertilization and ovulation induction combined with intrauterin insemination.

OBJECTIVE: To investigate the effect of sperm mucus penetration tests (SPT) on the fertilization rate (FR) and pregnancy rate (PR) in patients treated with either in vitro fertilization (IVF) or ovulation induction combined with intrauterine insemination (OI + IUI). METHODS: Retrospective analysis of a regional Infertility Unit database. Infertile couples where the women had normal ovarian function and a normal pelvis at laparoscopy and her partner had normal seminology who had failed at least two SPTs who were treated with either IVF or OI + IUI. These patients were compared with similar couples in whom SPTs were satisfactory (SPT + ve). Group A (SPT + ve) consisted of 46 patients who underwent 78 treatment cycles of IVF and Group B (SPT - ve) comprised 31 patients who underwent 35 IVF cycles. Group C (SPT + ve) consisted of 39 patients who underwent 84 treatment cycles with OI + IUI, and Group D (SPT - ve) consisted of 15 patients who underwent 37 cycles with the same treatment. RESULTS: In patients treated with IVF, the FR and PR per embryo transfer were 77.0% and 20.0%, respectively in Group A, and 64.0% and 22.6%, respectively in Group B. The differences in FRs were statistically significant (p < 0.001) but there was no difference in the PRs. In patients treated with OI + IUI, the PR per cycle were 22.0% in Group C and 16.2% in Group D. CONCLUSION: The results indicate that SPT failure was associated with a lower FR in IVF but this did not affect the PRs. Similarly there was no difference in PRs following OI + IUI.

Adult↗
PubMed1996

Risk perception and symptom reporting.

Public reaction to chemical technologies has included a perception that chemical exposure is a contributor to human health problems. Though these perceptions sometimes correspond with technical assessments of chemical risks, at other times they do not. This paper presents a descriptive model of the relationship between perception of one's health status and a set of factors that are used by individuals as part of causal reasoning about the meaning of somatic change. The model incorporates both personal events and experiences associated with somatic change (e.g., stress, sensory cues), as well as aspects of an individual's social context in which perceptions of chemical risks serve as a powerful framework for attributing meaning to chemical exposure. Within this model, the causal inferences that people make about the effects of chemical exposure on symptomatology are viewed as part of a natural, psychological adaptation in which the individual seeks to decrease their uncertainty about the factors or conditions that cause them to feel as they do.

Adaptation, Psychological↗
PubMed1995

Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility.

The aim of this prospective randomized controlled study was to determine the possible role of ovulation induction with intrauterine insemination (IUI) in the treatment of unexplained infertility. A total of 100 patients were randomized to receive ovulation induction with or without IUI. All patients were treated with long-course gonadotrophin-releasing hormone analogue (GnRHa), starting in the luteal phase, and exogenous follicle stimulating hormone (FSH) to induce follicular growth. Ovulation was induced using human chorionic gonadotrophin and timed intercourse (TI) was advised 24-48 h later or IUI was effected 36-48 h later. Both the cycle fecundities (21.8 and 8.5%) and the cumulative ongoing pregnancy rates after three cycles (42 and 20%) were significantly higher (P < 0.03) in the IUI group than in the TI group respectively. This is a clear indication that ovulation induction with IUI is an effective treatment method for unexplained infertility, but ovulation induction with TI has a negligible impact in this large group of patients.

Adult↗
PubMed1995

Pregnancy outcome following exposure to gonadotrophin-releasing hormone analogue during early pregnancy: comparisons in patients with normal or elevated luteinizing hormone.

The outcomes of established pregnancies following the treatment of infertile women with pituitary down-regulation before and during treatment with ovulation induction and either intrauterine insemination or timed intercourse were reviewed. Once started on gonadotrophin-releasing hormone analogue (GnRHa) treatment, the patients were maintained on GnRHa therapy throughout the following luteal phase to facilitate the start of the next treatment cycle if no pregnancy was established. This resulted in patients taking GnRHa until a positive pregnancy test indicated cessation of the treatment. The aim of our study was to determine whether exposure to GnRHa during early pregnancy constituted a risk. Patients who were diagnosed as having elevated follicular phase luteinizing hormone (LH) concentrations during their investigations were analysed as a separate cohort to assess whether this diagnosis had implications with respect to pregnancy outcome. Out of 226 recorded clinical pregnancies, 173 were traced and the data collated: 16 cases resulted in clinical abortions, two were ectopic pregnancies and 155 women had live births at various ages of gestation. There were three pregnancies which were complicated by congenital abnormalities. Patients with elevated LH concentrations on examination showed a higher rate of total pregnancy loss than those with normal LH concentrations, despite the fact that the LH was suppressed during the cycle in which they conceived. The results suggest that pregnancy outcome is not adversely affected by GnRHa administration during the luteal phase of the conception cycle, and that the group diagnosed as having elevated LH concentrations may retain their propensity to higher rates of pregnancy loss even when their LH concentrations are suppressed during treatment.

Adult↗
PubMed1995

A comparison of two starting doses of human menopausal gonadotrophin for follicle stimulation in unselected patients for in-vitro fertilization.

Ovarian responses and embryology data were compared in patients undergoing in-vitro fertilization following follicular stimulation using long course gonadotrophin-releasing hormone (GnRH) analogue/human menopausal gonadotrophin (HMG) in which the initial daily dose was two (150 IU) or three ampoules (225 IU) maintained for a minimum of 7 days. Group 1 (n = 31; centre A) patients were treated with a starting dose of two ampoules, while group 2 (n = 46; centre A) patients were treated chronologically immediately before group 1 with a starting dose of three ampoules per day. Group 3 (n = 74; centre B) patients were treated with three ampoules per day simultaneously with group 1. There was no difference in the distributions of patient ages or reasons for treatment between the three groups. Group 1 required longer treatment before the plasma oestradiol attained 250 pg/ml than did both the other groups (group 1, 9.0; group 2, 6.9; group 3, 6.7 days; P < 0.01), and this resulted in a longer follicular phase for group 1 (mean: 14.5 days compared with 12.7 and 12.8 for groups 2 and 3 respectively; P < 0.05). The numbers of follicles > 16 mm in diameter at human chorionic gonadotrophin (HCG) administration and the numbers of eggs and embryos were all significantly lower (P < 0.04) in group 1, and cycle cancellations due to insufficient ovarian responses were higher (P < 0.02) in group 1. There was no difference in the numbers of ampoules used, the oestradiol concentration at HCG, the fertilization and pregnancy rates or the incidence of hyperstimulation syndrome in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Spontaneous follicular and luteal function in infertile women with oligomenorrhoea: role of luteinizing hormone.

OBJECTIVE: There is a paucity of longitudinal endocrine studies of infertile patients with oligomenorrhoea. We have assessed the frequency and quality of spontaneous follicular development and luteal function in patients with oligomenorrhoea and infertility (PCOS), and have related the observed criteria to circulating LH activity. DESIGN: Prospective detailed investigations in a cohort of unselected patients. PATIENTS: Infertile women with oligomenorrhoea (PCOS, n = 131) presenting to the infertility clinic at the Royal Infirmary, Glasgow. MEASUREMENTS: Patients were monitored with frequent plasma oestradiol (E2) concentration assessments over a minimum period of 3 weeks, starting more than 2 weeks after a menstrual bleed. When follicular maturation was identified the patient provided daily blood samples through to her ensuing menstrual bleed, and E2, progesterone, total testosterone, FSH and LH were assessed in these samples. Luteal phase progesterone profiles were assessed between the days LH surge +2 and LH surge +6 by means of a progesterone index. RESULTS: Forty-eight per cent of the patients showed evidence of follicular development. The oestradiol profiles in the patients showing follicular growth were normal, but the progesterone curve was sub-normal in the early luteal phase, due to a high proportion of deficient luteal phases. The mean LH concentrations were elevated in the whole group, but no difference was observed between the mean LH values for those patients showing spontaneous follicular development and those who did not, and the incidence of ovulation was similar in the normal LH and elevated LH groups. Similarly, no relation was established between LH and the quantitative assessment of luteal phase progesterone profiles (progesterone index), and the distribution of progesterone indices was similar in the normal LH and elevated LH groups. Testosterone concentrations were positively correlated with LH (p = 0.008) but not with the incidence of spontaneous follicular growth. There was no significant difference in the incidence of spontaneous ovulation between the patients with elevated or normal mean follicular phase testosterone concentrations. CONCLUSION: The data indicate that both LH and testosterone secretion in PCOS were closely linked, but that neither was directly linked to the incidence or inhibition of spontaneous follicular development in PCOS, or to the disturbance in luteal phase progesterone profiles.

Adult↗
PubMed1995

[Population study of dihydropyrimidine dehydrogenase in cancer patients].

Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme of 5-fluorouracil (5-FU) catabolism. The clinical importance of DPD has recently been demonstrated with the identification of severe and/or lethal 5-FU-related toxicity in patients with suspected or proven DPD deficiency revealed in lymphocytes. We conducted a prospective study on 185 cancer patients in order to evaluate the incidence of complete or partial DPD deficiency. The population comprised 152 men (mean age 62.1) and 33 women (mean age 59.2). Sixty eight were head and neck patients treated by a 5-day continuous infusion of 5-FU (starting dose 1 g/m2/day, with dose adaptation at mid-cycle) for which DPD activity was measured 2-3 days before 5-FU administration (94 cycles analyzed). DPD activity was measured by a radioenzymatic assay using 14C-5-FU. DPD activity showed a unimodal distribution, which globally fits a Gaussian distribution. Mean and median DPD activity were 0.222 and 0.211 nmol/min/mg prot respectively (range 0.065-0.559). No total DPD deficiency was found. Neither liver function nor age influenced DPD activity, but DPD activity was on average 15% lower in women than in men (0.194 and 0.228 nmol/min/mg prot respectively, p = 0.03). In patients treated with 5-FU, the risk of developing side effects was not linked to pretreatment DPD activity. 5-FU-related toxicity was linked to FU systemic exposure. The correlation between DPD activity and FU clearance was weak (n = 90, r = 0.31, p = 0.002). As a corollary, DPD activity in patients requiring a dose reduction was not significantly different from DPD activity in patients who did not require dose modification. From the present study it appears that total DPD deficiency is a very rare event. Although pre-treatment DPD activity cannot be a useful indicator for improving 5-FU dose adaptation strategy, the identification of partial DPD deficiency (< 0.100 nmol/min/mg prot, 3% of the population) could lead to starting the treatment with a markedly reduce 5-FU dose.

Adult↗
PubMed1994

Ovarian stimulation in an infertile patient with growth hormone-deficient Oliver-Mcfarlane syndrome.

Several authors have suggested that growth hormone may augment ovarian responses to follicle stimulating hormone in women (Homburg et al., Clin. Endocrinol., 29, 1988; Ibrahim et al., Fertil. Steril., 55, 1991), and that this effect may be mediated by insulin-like growth factor I (IGF-I) (Davoren and Hsueh, Endocrinology, 118, 1986). Menashe et al. (Hum. Reprod., 6, 1991) reported spontaneous pregnancies in women with a deficiency in growth hormone receptors and, consequently, low serum concentrations of IGF-I. In this report, we present the case of a patient with a rare syndrome first described by Oliver and Mcfarlane (Arch. Ophthalmol., 74, 1965). The patient was shown to be growth hormone deficient, with hypopituitarism as part of the syndrome. Adjuvant growth hormone did not influence her ovarian responses to exogenous gonadotrophins during assisted conception treatment, as reflected by the required total number of ampoules of human menopausal gonadotrophin, the number of developing follicles, the rate of follicular growth and the serum oestradiol concentrations.

Adult↗
PubMed1994

Population study of dihydropyrimidine dehydrogenase in cancer patients.

PURPOSE: We conducted a prospective study on a large set of cancer patients in an attempt to evaluate the incidence of complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency as found in peripheral mononuclear cells (PMNC). PATIENTS AND METHODS: One hundred eighty-five unselected consecutive cancer patients were included. The population consisted of 152 men (mean age, 62.1 years; range, 35 to 90) and 33 women (mean age, 59.2 years; range, 36 to 77). Sixty-eight were head and neck patients treated by a 5-day continuous infusion of fluorouracil (FU; starting dose, 1 g/m2/d, with dose adaptation based on pharmacokinetics) for which DPD activity was measured 2 to 3 days before FU administration (94 cycles analyzed). PMNC-DPD activity was measured by a radio-enzymatic assay using carbon-14-FU. RESULTS: DPD activity in the entire population showed a unimodal distribution, which globally fits a gaussian distribution. Mean and median DPD activity values were 0.222 and 0.211 nmol/min/mg protein, respectively (range, 0.065 to 0.559). No total DPD deficiency was found. Multifactor analysis of variance showed that liver function (biologic evaluation) and age did not influence DPD activity, but that DPD activity was, on average, 15% lower in women (0.194 nmol/min/mg protein) than in men (0.228 nmol/min/mg protein) (P = .03). No difference was demonstrated between premenopausal and postmenopausal women. In patients treated with FU, the risk of developing side effects was not linked to pretreatment DPD activity. FU-related toxicity was linked to FU systemic exposure. The correlation between pretreatment DPD activity and FU systemic clearance (CI) was weak (n = 90, linear regression r = .31, P = .002). Pretreatment DPD activity in patients who required a dose reduction was not significantly different from DPD activity in patients who did not require dose modification. CONCLUSION: From the present study, it appears that total DPD deficiency is a rare event. Although pretreatment DPD activity cannot be a useful indicator for improving FU dose adaptation strategy, the identification of severe DPD deficiency (< 0.100 nmol/min/mg protein) could lead to starting the treatment with a markedly reduced FU dose or even to using an alternative chemotherapy regimen.

Adult↗
PubMed1993

A search for C60 in carbonaceous chondrites.

Analysis of interior samples of the Murchison meteorite by two routes yielded an upper limit of 2 ppb for its C60 content, as compared to parts per million levels for individual polycyclic aromatic hydrocarbons (PAHs). Provided the samples contain an interstellar component, which is probable since Murchison hydrocarbons contain excess deuterium, this result argues against the ubiquitous presence of C60 in the interstellar medium. A possible explanation for the absence of C60 was found in experiments showing how PAHs replace fullerenes as stable end products when hydrogen is present during carbon condensation. As a secondary result we found high molecular weight PAHs in the Murchison and Allende meteorites. Coronene and its methyl derivatives are especially interesting since features in the coronene spectrum have been shown to match some of the unidentified interstellar infrared emission bands.

Carbon↗
PubMed1993

Assessments of embryo transfer after in-vitro fertilization: effects of glyceryl trinitrate.

The role of embryo transfer and its associated difficulties on the outcome of human in-vitro fertilization (IVF) were examined using a standardized procedure and a scoring system (embryo transfer scores 1-5). This system was used to assess any effects of the smooth muscle relaxant glyceryl trinitrate (GTN) on embryo transfer. Patients (n = 120) were randomized in a double-blind manner at their first embryo transfer to receive sublingual GTN or placebo before the transfer. Retrospective analysis showed that higher pregnancy rates were associated with uncomplicated transfers (score 1; P < 0.01). The outcome measures included pregnancy rate, total time of cervical manipulation (embryo transfer time) and embryo transfer score. All pregnancies had a transfer score of 1 or 2, but no recorded parameter differentiated between pregnant or non-pregnant cycles, and GTN had no significant effect on any parameter.

Cervix Uteri↗
PubMed1992

Absence of effect of adjuvant growth hormone therapy on follicular responses to exogenous gonadotropins in women: normal and poor responders.

OBJECTIVE: To examine the effects of growth hormone (GH) on ovarian responses to exogenous gonadotropins after pituitary desensitization in normal and poor responder patients undergoing in vitro fertilization. DESIGN: A prospective study with comparison of control and GH-treated cycles. PATIENTS: Poor responder patients (n = 10) required > 44 ampules of human menopausal gonadotropin (hMG) to achieve criteria for administration of human chorionic gonadotropin (hCG) on day 0 or cancellation in control cycles, and normal responder patients (n = 10) required < 45 ampules. MAIN OUTCOME MEASURES: Ovarian responses to hMG assessed by duration of stimulation required to achieve first significant estradiol (E2) response and hCG criteria. Total doses and duration of hMG, follicular development and E2 concentrations on day 0, and embryology were also assessed. RESULTS: Growth hormone showed no effect on any of the parameters studied in either patient group. CONCLUSION: Follicular recruitment, E2 secretion by mature follicles, and oocyte yield and quality were uninfluenced by GH treatment.

Adult↗