Research of the Holiday kind. Case report: microcardia secondary to chronic adrenocortical insufficiency.
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Wit and Humor as Topic↗
Biomedical subjects
R Fleming
Publications and source records attributed to R Fleming.
Ethanol and neurosteroid interactions in the brain.
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Alcoholism↗
Two unbalanced translocations involving a common 6p25 region in two XY female patients.
We report two 46,XY female patients with two different de novo unbalanced translocations, each involving the chromosomal region 6p25. The patient with a 46,XY,der(6)t(X;6)(p21.2;p25) karyotype had a sex reversal phenotype. The patient with a 46,XY,der(13)t(6;13)(p25;q33) karyotype had a male pseudohermaphrodite phenotype. Multi-paint fluorescent in situ hybridization was performed to determine the origin of the derivative material on 6p and 13q. The association of abnormalities of the 6p25 region with either an Xp duplication or a 13q deletion is reported here for the first time.
Adolescent↗
Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters.
OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit an abnormal lipoprotein profile, characterized by raised concentrations of plasma triglyceride, marginally elevated low density lipoprotein (LDL)-cholesterol, and reduced high density lipoprotein (HDL)-cholesterol. However, a normal LDL-cholesterol level may be misleading since LDL exists as subpopulations of particles differing in size and atherogenic potential. Smaller LDL particles are more atherogenic and high concentrations often occur in association with elevated circulating triglyceride concentrations (but frequently normal total LDL-cholesterol), increased hepatic lipase activity (HL) and insulin resistance. Information on LDL subclasses and HL activity in women with PCOS is sparse. The aim of this study was to determine the concentrations of small, dense LDL (LDL-III) in women with PCOS relative to body mass index (BMI)-matched controls. We also examined the association of lipoprotein subfraction concentrations with endogenous sex hormone concentrations, since existing literature suggested that androgens up-regulate and oestrogens down-regulate HL activity, a key determinant of LDL subfraction distribution. DESIGN: Cross sectional study. PATIENTS: Fifty-two women with oligomenorrhoea and polycystic ovaries determined by ultrasound and BMI matched women with normal menstrual rhythm (NMR) and normal ovarian appearances (n = 14) were recruited from gynaecology clinics. Anthropometric data and fasting blood samples were obtained for metabolic, hormonal and LDL subfraction estimation and a heparin provocation test was used to estimate HL activity. RESULTS: Subjects with PCOS demonstrated higher waist:hip ratio (WHR), testosterone, triglyceride, VLDL-cholesterol concentrations, and HL activity (P < 0.05), whereas SHBG concentrations were significantly lower than controls. PCOS women had higher concentrations (38.0 vs. 25.0 mg/l; P = 0.026) and proportions (12.8 vs. 8.2%; P = 0.006) of small, dense LDL (LDL III), relative to controls. Within the PCOS group, plasma triglyceride and HL activity were the strongest univariate predictors of LDL III mass. They remained as independent predictors in multivariate analysis, and together accounted for 37% of its variability (P = 0.0002). Independent predictors of plasma triglyceride and HL in turn, were measures of fat distribution (waist circumference or WHR) and fasting insulin concentration. Serum testosterone concentration was not associated either in univariate or multivariate analysis with any of the measured lipid, lipoprotein or subfraction parameters, nor with HL activity in the women with PCOS. CONCLUSION: We conclude that women with polycystic ovary syndrome have increased hepatic lipase activity and mass and percentage of small, dense low density lipoprotein relative to body mass index-matched controls with normal menstrual rhythm and normal ovaries. Further, these metabolic perturbances appear related more closely to adiposity/insulin metabolism than to circulating androgen levels.
Adult↗
Mandibular and palatal tori, bone mineral density, and salivary cortisol in community-dwelling elderly men and women.
BACKGROUND: This investigation evaluated the relationship between the presence of tori and bone mineral density (BMD) and salivary cortisol levels. METHODS: A total of 230 healthy, community-dwelling elderly men (n = 129) and women (n = 101) aged 60 and older participated in this study. Forty-three women were on hormone replacement therapy (HRT). This was a component of a 5-year longitudinal study measuring subjects' body composition, hormone levels, physical activity, and diet every 6 months. Subjects were examined for the presence of tori by visual inspection and digital palpation. BMD at six sites was measured by dual-energy X-ray absorptiometry. Salivary cortisol levels were measured by radioimmunoassay. RESULTS: Twenty-three percent of all subjects had mandibular tori, 13% had palatal tori, and 12% had both mandibular and palatal tori. Mandibular tori were more common in men, and palatal tori were more common in women. The presence of mandibular tori was significantly correlated with BMD of the lumbar spine, femoral neck, trochanter, and Ward's triangle for all subjects, and with the femoral neck and trochanter of women not on HRT. Men with palatal tori had lower levels of salivary cortisol in the evening. CONCLUSIONS: This study documented the high prevalence of mandibular and palatal tori in a group of 230 elderly, community-dwelling subjects. Women not on HRT and all subjects taken as a group with mandibular tori had higher BMD. The presence of tori at young adulthood may be a marker of higher BMD in the future and of a lower risk for developing osteoporosis.
Aged↗
Circulating leptin concentrations and ovarian function in polycystic ovary syndrome.
OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction. Although the role of leptin in the control of reproduction is unclear, it may be involved in the control of ovulation. The aim of this cross-sectional study was to determine the relationship between circulating leptin concentrations, and anthropometric, metabolic and endocrine variables as well as to examine a possible role of leptin in ovarian dysfunction associated with PCOS. DESIGN: Prospective observational study. METHODS: Seventy-one subjects with PCOS and 23 body mass index (BMI)-matched control subjects were recruited from infertility clinics. The association between serum leptin concentrations and the above variables was measured outwith the luteal phase. A subgroup of 24 PCOS subjects underwent more frequent blood sampling to monitor follicular growth and ovulation. The association between variables was measured by univariate, multivariate and partial correlation analyses. RESULTS: Serum leptin concentrations were not different in subjects with PCOS and controls, and were strongly associated with BMI in both groups. Twelve patients ovulated during the study period. There was no significant difference in serum leptin concentrations between ovulatory and anovulatory subjects. The relationship between BMI and leptin was similar in both groups. CONCLUSION: The results indicated that circulating leptin concentrations relate principally to total body fat in subjects with PCOS and controls, and that this is not associated with the facility for follicular development and ovulation in these patients.
Adult↗
Suppression of LH during ovarian stimulation: effects differ in cycles stimulated with purified urinary FSH and recombinant FSH.
There has been much debate about the role of luteinizing hormone (LH) during follicle stimulating hormone (FSH)-treated ovarian stimulation for assisted reproduction, where the endogenous LH is suppressed using a gonadotrophin-releasing hormone analogue. The requirement for LH in oestradiol biosynthesis is established, but other effects of 'insufficiency' are less clear, and little attention has been paid to the specific origin of the FSH used. The aim of this study was to examine the roles of profoundly suppressed circulating LH concentrations in cycles of ovarian stimulation for IVF, which were affected in two large separate cohorts of patients undergoing assisted reproduction. They were stimulated by either purified urinary FSH (MHP) or recombinant human FSH (rFSH). Within each dataset, outcomes were examined with respect to the circulating concentrations of LH in the mid-follicular phase, as plasma samples were stored prospectively, and assayed retrospectively. Patients with profoundly suppressed LH showed much reduced oestradiol concentrations at mid-follicular phase and at human chorionic gonadotrophin administration in cycles treated with either MHP or rFSH. However, gross ovarian response, as became evident by FSH dose demands, duration of stimulation, and also oocyte and embryo yields and embryo cryopreservation were influenced only in cycles treated with MHP. Furthermore, no effect upon pregnancy survival was observed. Thus, it is concluded that there is a demand for additional exogenous LH treatment only in cycles treated with purified urinary FSH where the LH is profoundly suppressed.
Abortion, Spontaneous↗
Fourier transform infrared spectroscopy of follicular fluids from large and small antral follicles.
Fourier transform infrared spectroscopy (FTIR) was used to obtain 'biochemical fingerprints' for the constitution of follicular fluids from large and small antral luteinized follicles (n = 54 pairs). All samples gave reproducible characteristic biological infrared absorption spectra, with recognizable amide I protein vibrations and acyl vibrations from fatty acids. Discriminant function analysis of the first derivative FTIR spectra, together with hierarchical cluster analysis used to construct a dendrogram, showed fluid from large follicles formed a homogeneous closely related cluster, whilst that from small follicles was distinct from the large, and heterogeneous in nature. The large follicle fluids showed closer biochemical similarity to each other than to the corresponding fluid taken from small matched follicles. An artificial neural network was trained and following validation with an independent test set, successfully distinguished follicular fluids from large and small follicles. The sex steroid concentrations in the fluids from large and small follicles were significantly different. These results show that fluid from large follicles is distinct in biochemical nature from that from small follicles, but the degree of homogeneity implies size-specific changes take place. These may have consequences for the developmental potential of the oocyte.
Discriminant Analysis↗
Detection of plant genes using a rapid, nonorganic DNA purification method.
We have developed a simple procedure for the preparation of plant genomic DNA using FTA paper. Plant leaves were crushed against FTA paper, and the genomic DNA was purified using simple, nonorganic reagents. The 18S rRNA gene and the gene encoding the ribulose-1, 5-bisphosphate carboxylase/oxygenase large subunit (rbcL) from the chloroplast genome were detected by PCR amplification of DNA on FTA paper. DNA amplification was successful using extracts from 16 dicot and monocot plants. Studies of specific plant extracts revealed that extracts of leaf samples could be collected and stored at room temperature on FTA paper without a decrease in the DNA amplification success rate for more than a month. Both the 18S RNA gene and the rbcL gene were detected in the genomic DNA isolated from various soybean cultivars stored in this manner. Furthermore, by modestly increasing the number of cycles of DNA amplification, we were able to detect the uidA gene in transgenic tobacco and rice leaves as well as a single copy gene linked to the resistance gene of cyst nematode race 3 using genomic DNA isolated on FTA paper. These results demonstrate that genomic DNA isolated using FTA paper can be used for the detection of plant genes, from a wide range of plants with either high or low gene copy number and of either nuclear or cytoplasmic origin.
Base Sequence↗
Horace townshend fleming
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Journal Article↗
Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea.
Hyperinsulinaemic insulin resistance is commonly associated with hyperandrogenaemia, and menstrual dysfunction. The aim of this study was to examine the effects of the insulin sensitizing drug, metformin, on ovarian function, follicular growth, and ovulation rate in obese women with oligomenorrhoea. Twenty obese subjects with oligomenorrhoea [polycystic ovarian syndrome; (PCOS)] were observed longitudinally for 3 weeks prior to and for 8 weeks during treatment with metformin (850 mg twice per day). Fifteen patients completed the study. The frequency of ovulation was significantly higher during treatment than before treatment (P = 0.003). A significant decline in both testosterone and luteinizing hormone concentrations was recorded within 1 week of commencing treatment. Patients with elevated pretreatment testosterone concentrations showed the most marked increase in ovulation rate (P < 0.005), and significant reductions in circulating testosterone from 1.02 to 0.54 ng/ml (P < 0.005) after only 1 week of treatment. However, the sub-group with raised fasting insulin showed less marked changes, and the sub-group with normal testosterone concentrations showed no effect of treatment. Metformin had a rapid effect upon the abnormal ovarian function in hyperandrogenic women with PCOS, correcting the disordered ovarian steroid metabolism and ovulation rate; however, there appeared to be no effect in cases where the circulating androgen concentration was normal.
Adult↗
Polycystic ovarian syndrome: the metabolic syndrome comes to gynaecology.
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Cardiovascular Diseases↗
Luteinizing hormone increases estradiol secretion but has no effect on progesterone concentrations in the late follicular phase of in vitro fertilization cycles in women treated with gonadotropin-releasing hormone agonist and follicle-stimulating hormone.
OBJECTIVE: To determine whether the late follicular phase increase in circulating P concentrations during controlled ovarian stimulation with GnRH-a and FSH can be influenced by addition of LH to the stimulating gonadotropin during the final 2 days. DESIGN: Randomization of patients to receive either FSH alone or FSH with LH (hMG) for the final 2 days before hCG, after follicular phase stimulation with purified FSH. SETTING: A.C.S. Unit at the Royal Infirmary, Glasgow, U.K. PATIENT(S): Patients were unselected and were undergoing IVF. INTERVENTION(S): Patients received stimulation with purified FSH (300 IU/d) until a follicle of 15 mm was observed; the regimen was then changed to either 225 IU of FSH or 225 IU of hMG. MAIN OUTCOME MEASURE(S): Estradiol and P in the peripheral circulation. RESULT(S): Significant increases in E2 concentration were observed, but there were no changes in the circulating progesterone. CONCLUSION(S): The late follicular phase increase in P is unrelated to any luteinizing process attributable to effects in the circulation or sensitization of follicular cells to LH.
Adult↗
Effect of profound suppression of luteinizing hormone during treatment with gonadotrophin-releasing hormone analogue and purified follicle stimulating hormone upon development of cryopreserved embryos.
In response to previously published evidence from monkeys, this study examined the influence of the degree of luteinizing hormone (LH) suppression during the follicular phase of the stimulation cycle, upon cryopreserved embryo survival and development. The LH concentration of the mid-follicular phase was assessed in 250 in-vitro fertilization (IVF) cycles treated with gonadotrophin-releasing hormone analogue (GnRHa) and either purified follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG), and was related to the performance of cryopreserved embryos in 351 subsequent embryo transfer cycles. Rates of embryo survival, embryo development rates, implantation rates, and pregnancy rates were examined with respect to the LH concentration recorded in the mid-follicular phase. In contrast to experimental evidence from other primates, there was no significant influence of the follicular phase LH concentration upon any of the parameters examined.
Cryopreservation↗
Effects of profound suppression of luteinizing hormone during ovarian stimulation on follicular activity, oocyte and embryo function in cycles stimulated with purified follicle stimulating hormone.
The effects of profound suppression of circulating luteinizing hormone (LH) during the follicular phase of in-vitro fertilization cycles were explored in normal women during treatment with a gonadotrophin-releasing hormone analogue and exogenous purified follicle stimulating hormone. Ovarian responses to treatment and the capacity of supernumerary embryos to undergo blastocyst formation were examined in groups of patients defined by the concentration of plasma LH in the mid-follicular phase. Concentrations < or = 0.5 IU/I diagnosed the group with profoundly suppressed LH (<LH, n = 20), which was compared with the remaining patients (nLH, n = 41). The <LH group showed lower oestradiol concentrations at human chorionic gonadotrophin administration, while the total follicular development estimated by the total follicular diameters was similar in both groups. The oestradiol secreted per follicle, estimated by the circulating concentration per mm total follicular diameter, was significantly lower in the <LH group. The combined effects of a trend to lower yield of oocytes (not significant) and a lower fertilization rate (not significant) resulted in a significantly reduced quantity of embryos available for cryopreservation after the fresh transfer. Supernumerary embryos were cultured for 7 days to determine blastocyst development rates, and the degree of LH suppression made no difference to embryo developmental competence (nLH, 23%; <LH, 27%), or the rates of blastocyst formation. The group of patients with profoundly suppressed mid-follicular phase LH showed a reduced yield of oocytes and embryos which resulted in significantly fewer embryos available for cryopreservation. However, the developmental potential of those embryos, represented by the ability to form blastocysts in vitro, was unaffected.
Adult↗
Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in pre-eclampsia.
OBJECTIVE: To determine whether vascular endothelial growth factor (VEGF) concentrations are altered in pre-eclampsia. DESIGN: Serum was prepared from peripheral venous blood and stored at -70 degrees C. Serum VEGF concentrations were measured by ELISA. SETTING: University of Glasgow Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. PARTICIPANTS: Twenty-two healthy nonpregnant volunteer women, 34 normal pregnant women and 34 women with pre-eclampsia were studied. RESULTS: Serum concentrations of VEGF were significantly lower in normal pregnant women (median value 12.89 pg/mL) than in nonpregnant women (median value 166 pg/mL; P < 0.0001). In pre-eclampsia VEGF concentrations were significantly lower (median value 2.34 pg/mL) than normal pregnancies (P < 0.0001). Postpartum concentrations of VEGF in the group complicated by pre-eclampsia (median value 76.42 pg/mL) were not significantly different from nonpregnant values (P = 0.2). CONCLUSIONS: Our results show that serum concentrations of VEGF are suppressed in pregnancy and further reduced in pre-eclampsia. Further studies to elucidate the mechanisms which lead to a reduction in VEGF concentrations may provide new clues to the aetiology of this disorder.
Adult↗
The predictive value of the sperm-cervical mucus interaction test on the outcome of in vitro fertilization and ovulation induction combined with intrauterine insemination.
We investigated the effect of the sperm-cervical 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). 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 2 SPTs 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. 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 difference in FRs was 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. These 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.
Female↗
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↗