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Biomedical subjects

H W Jones

Publications and source records attributed to H W Jones.

At least 37 records · Page 2Linked to original sources

Variations in plasma levels of substance P and effects of a specific substance P antagonist of the NK(1) receptor on preovulatory LH and FSH surges and progesterone secretion in the cycling cynomolgus monkey.

These studies investigated the role of substance P (SP) in the regulation of the hypothalamic-pituitary-ovarian axis in cynomolgus monkeys with normal menstrual cycles. Plasma concentrations of SP were determined in blood samples taken every morning in normally menstruating cynomolgus monkeys throughout the menstrual cycle. There was a significant decreasing linear trend of SP during the follicular phase (cycle day -13 to day 0) and a significant inverse relationship between SP plasma values and plasma 17beta-estradiol (E(2)) values from day -13 to day 0 of the adjusted cycle. Correspondingly, SP area under the curve was significantly greater during the follicular phase than the luteal phase. In a second experiment, plasma concentrations of E(2), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone and length of cycles were measured after five daily intragastric administrations (10 mg/kg) of an NK(1) receptor (SP receptor) antagonist (RPR 100893; 10 mg/kg) initiated after serum E(2) concentrations had exceeded 125 pg/ml. There was a statistically significant reduction in the amplitude (41% of control) and the area under the curve (37% of control) of the preovulatory LH surge. In addition, there was a reduction of the duration of the LH surge (3 +/- 0.1 days in controls vs. 2.1 +/- 0.2 days in treated animals). The present results show for the first time that there are significant variations in plasma levels of SP, with a strong negative correlation with serum levels of E(2) during the follicular phase of the cynomolgus monkey, and that endogenous SP has a potentiating role in the interactive hypothalamo-anterior-pituitary mechanisms which lead to the preovulatory LH and FSH surges during the menstrual cycle in the monkey.

Animals↗

Endometrial estrogen and progesterone receptor and pinopode expression in stimulated cycles of oocyte donors.

OBJECTIVE: To study the effect of controlled ovarian hyperstimulation and the ovarian response on several features of endometrial morphology simultaneously. DESIGN: Prospective controlled study. SETTING: Academic infertility center. PATIENT(S): Twenty-five oocyte donors undergoing COH and 10 ovulatory controls. INTERVENTION(S): Endometrial biopsies during the luteal phase and measurement of serum E2 and progesterone levels on days 12, 13, and 18-20. MAIN OUTCOME MEASURE(S): Endometrial morphology as judged by histologic dating, pinopode expression, and estrogen and progesterone receptor content. RESULT(S): Controlled ovarian hyperstimulation caused the early expression of endometrial features as judged by histologic dating criteria, estrogen and progesterone receptor expression, and the timing of pinopode expression in many of the subjects. A significant correlation within subjects with regard to their particular result on any one measure (e.g., histologic examination) and the others (e.g., estrogen and progesterone receptors, pinopodes) was observed. Those with higher levels of progesterone the day after hCG administration exhibited the most prematurity of morphologic features. CONCLUSION(S): Many controlled ovarian hyperstimulation cycles are associated with synchronous early expression of the expected pattern of histologic features, estrogen and progesterone receptors, and pinopodes. The most predictive feature of this premature expression was the level of progesterone the day after hCG administration.

Biopsy↗

New reproductive technologies.

The ethical calculus is described. There are four entities that have a stake in all ethical decisions. These are the individual, family, community and society at large. Values assigned to these entities can be modified by experience, cultural background, religious authority and the law. In the simple case of in vitro fertilization (IVF), there seems to be general international acceptance, except for the official position of the Roman Catholic Church, the origin of which dissent is extensively discussed. There is concern about the number of pre-zygotes/pre-embryos to be transferred, the disposition of any unfertilized egg and the reporting of results. Clear ethical considerations arise as IVF is applied in more complex situations, such as unmarried couples, the use of donor gametes and donor pre-embryos, the use of cryopreservation, intracytoplasmic sperm injection (ICSI), prenatal genetic diagnosis, surrogate gestational motherhood and research on the pre-embryo. The ethical, religious and legal acceptance of these depends on the weight given to elements of the ethical calculus as described in the chapter.

Ethics, Medical↗

Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles.

The formation of endometrial pinopodes detected by scanning electron microscopy may be a specific marker for uterine receptivity. Aiming to assess the effects of ovarian stimulation on pinopode formation, we examined sequential endometrial biopsies from 17 oocyte donors. Seven normally menstruating women served as controls. Up to four samples were taken from each woman at 24-72 h intervals between days 14 and 24, giving a total of 69 samples. The day of oocyte retrieval was designated day 14 in ovarian stimulation cycles and the day of luteinizing hormone surge was designated day 13 in natural cycles. Endometrial morphology and pinopode numbers were similar in both groups. Fully developed pinopodes appeared in only one sample per cycle, indicating their short life span. However, the cycle day these structures appeared varied up to 5 days between women and the distribution was as follows: day 18 (n = 2), day 19 (n = 7), day 20 (n = 4), day 21 (n = 3), day 22 (n = 1) in ovarian stimulation cycles, and day 20 (n = 2), day 21 (n = 2), day 22 (n = 3) in natural cycles. Furthermore, accelerated pinopode formation in ovarian stimulation cycles was positively correlated with day 13 progesterone. Our findings show that ovarian stimulation does not affect endometrial pinopode formation in terms of quantity and life span. The cycle days when pinopodes form are specific to the individual, being on average 1-2 days earlier in ovarian stimulation than in natural cycles. These changes in pinopode expression may reflect shifts in the window of receptivity, resulting in ovo-endometrial asynchrony and limiting implantation success in in-vitro fertilization.

Adult↗

The psychological status at school age of children conceived by in-vitro fertilization.

This study assessed the behavioural and psychological profiles of children conceived by in-vitro fertilization (IVF) who are now at school age. A total of 743 IVF children born at one institution and now of school age, over 4 years old, were surveyed with Achenbach questionnaires. Follow-up telephone interviews were conducted with non-responders. The results from the study group were compared to the questionnaire control group using one-tailed t-test with statistical significance set less than 0.05. There was an 84% overall response rate. Sixty-seven per cent returned questionnaires. An additional 17% completed a telephone interview. The study group had no statistically significant increase in the rate of behavioural or psychological problems compared with the control group. There were no statistically significant differences within the study group related to sex or to multiple gestation IVF births. This large group of school-age IVF children has normal psychological development with no identified adverse effect of their status as IVF children. Determining the role, if any, of IVF in the very small number of children with behavioural and psychological problems will require additional study.

Adolescent↗

The detection of DNA from a range of bacterial species in the joints of patients with a variety of arthritides using a nested, broad-range polymerase chain reaction.

OBJECTIVE: Bacteria have been implicated in the pathogenesis of many types of inflammatory arthritides. The aim of this study was to identify any bacterial DNA in synovial fluid (SF) from patients with a range of inflammatory arthritides. METHODS: A highly sensitive, broad-range, nested polymerase chain reaction (PCR) protocol targeting the bacterial 16S rRNA gene was designed and applied to SF from 65 patients with a range of rheumatic diseases. RESULTS: Bacterial DNA was detected in 26 SF samples, including eight from patients with rheumatoid arthritis and five with juvenile arthritides. PCR products were identified by sequencing and searching of bacterial genomic databases; 'best fits' included Haemophilus influenzae, Bordetella and Yersinia. CONCLUSIONS: These finding suggest an association between bacterial infection and inflammatory arthritides in some patients. Further research is required to determine the role of these organisms in the pathogenesis and whether such patients might respond to prolonged antibiotic therapy.

Adolescent↗

Plasma substance-P and substance-K and gonadal steroids in relation to the gonadotropin surge in normal human reproductive cycles.

PURPOSE: This study was designed to examine changes in peripheral plasma substance-P and -K levels, their association with follicle-stimulating hormone and luteinizing hormone release in normal reproductive cycles in humans, and their correlation with plasma estradiol and progesterone. METHODS: Fourteen healthy, normally menstruating women underwent daily blood sampling (cycle day 4, 4-14 days) for measurement of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone, substances-P and -K, and daily transvaginal ultrasounds assessing follicular growth and documentation of ovulation. RESULTS: Estradiol peaked on day 13, luteinizing hormone and follicle-stimulating hormone peaked on day 14, and progesterone began an exponential increase on about day 13. CONCLUSIONS: In contrast to other experimental designs using in vitro or in vivo rat or monkey tissue, peripheral levels of substances-P (P = 0.8391) and -K (P = 0.3205) reflected no modulation related to midcycle gonadotropin release in cycling woman.

Adult↗

Inactivation of antithrombin III in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVE: To investigate the thrombin inhibitory capacity of antithrombin III in the inflamed human joint. METHODS: Thrombin inhibitory capacity was measured, using a kinetic spectophotometric method, in matched plasma and synovial fluid samples of patients with rheumatoid arthritis (n = 22) and osteoarthritis (n = 16), together with normal control plasma samples (n = 13). In the same samples, the concentration of antithrombin III was also determined by the method of radial immunodiffusion. The combination of these measurements allowed the calculation of the specific thrombin inhibitory capacity of these samples. RESULTS: An increased concentration of antithrombin III in rheumatoid compared with osteoarthritic synovial fluid was noted (p < 0.05). However, there was a significant depression in the specific activity of antithrombin III in rheumatoid synovial fluid when compared with matched plasma samples (p < 0.001) or with osteoarthritic synovial fluid (p < 0.05). CONCLUSION: In rheumatoid synovial fluid the thrombin inhibitory capacity of antithrombin III is disproportionately depressed relative to the concentration of antithrombin III, indicating the inactivation of antithrombin III in the rheumatoid joint.

Aged↗

An analysis of discharge drug prescribing amongst elderly patients with renal impairment.

Renal impairment is common amongst elderly patients and increases the risk of drug toxicity. Analysis of the discharge summaries of patients discharged from the geratology wards of an Oxfordshire hospital, showed that renal impairment was not referred to in 42% of patients with calculated creatinine clearances of 10-20 ml/min. A fifth of these patients, and 67% of patients with calculated creatinine clearances < 10 ml/min, had discharge drug prescriptions that contradicted the British National Formulary guidelines for prescribing in the presence of renal impairment. There should be increased awareness that, in elderly patients, normal serum creatinine concentrations do not exclude renal impairment and that several commonly prescribed drugs require dose adjustments or should be avoided in the presence of renal insufficiency.

Aged↗

Postoperative pelvic irradiation in early stage uterine mixed mullerian tumors.

PURPOSE OF INVESTIGATION: To review our management experience with uterine mixed mullerian tumors (MMTs) in order to evaluate potential prognostic indicators, and assess the efficacy of various treatment modalities. METHODS: A retrospective, clinicopathologic evaluation of 43 patients presenting for treatment of uterine MMTs between 1982 and 1992 was conducted. Diagnostic criteria for inclusion was the presence of both a malignant glandular or squamous epithelial component, and a homologous or heterologous stromal component. RESULTS: Overall 2- and 5-year cancer related Kaplan-Meier survival estimates with 95% confidence intervals were 44 (.28, .59) and 26% [.12, .39], respectively. Survivals were 83 [.62, .99] and 58% [.31, .85] when disease was confined to the uterus, and 22 [.03, .41] and 7% [.01, .20] when disease extended beyond the uterus. Clinical staging was often inaccurate, with 29% of clinical stage I or II disease being upstaged at laparotomy. A significant survival advantage was found in patients with stage I or II disease treated with surgery plus pelvic irradiation (p = 0.001), as compared to those treated with surgery alone. The prognosis after disease recurrence was poor, irrespective of secondary therapy, with a median survival of 11 months. CONCLUSIONS: A therapeutic advantage may be gained from postoperative pelvic irradiation in the treatment of surgical stage I or II uterine MMT.

Adult↗

ACTH, beta-endorphin, substance P, and corticotrophin releasing hormone in plasma and follicular fluid in hormonally stimulated menstrual cycles for in-vitro fertilization in the human.

Changes in plasma concentrations of ACTH, beta-endorphin (beta-EP) and cortisol have been found to be associated during the human menstrual cycle. Changes in hypothalamic levels of gonadotrophin releasing hormone (GnRH), beta-EP and substance P (SP) have also been associated with the oestrous cycle in the rat. Therefore, an attempt was made to measure the activity of the corticotrophic axis and SP by measuring blood and follicular fluid concentrations of ACTH, beta-EP, SP and corticotrophin releasing hormone (CRH) during the hormonal ovarian stimulation phase for in-vitro fertilization (IVF), in a series of 19 patients. At the plasma level, there was no significant change over treatment days in ACTH (P = 0.1550), beta-EP (P = 0.1137), or SP concentrations (P = 0.5625). CRH was not detectable over treatment days. In addition, there was no significant change in neuropeptide over treatment days between those women who became pregnant and those who did not (P = 0.17 for all). In the follicular fluid, ACTH was not detectable, beta-EP concentration was three times higher than in the plasma, CRH was detectable, and SP concentration was similar to that of plasma. There was no apparent correlation, however, between beta-EP or SP concentrations in the plasma and follicular fluid from a given patient. In conclusion, the absence of changes in the activity of the corticotrophic axis during the hormonal ovarian stimulation suggests that there was no major stress component associated with the stimulation phase of IVF or the occurrence of a pregnancy.

Adrenocorticotropic Hormone↗

Cryopreservation: a simplified method of evaluation.

A theoretical model is presented by which a true expression of pregnancy rate resulting from stimulated cycles can be calculated. This includes the transfer of both fresh and cryopreserved embryos. It is concluded that the total reproductive potential of a single cycle of stimulation can only be evaluated by including pregnancies arising from all fresh and frozen embryo transfers resulting from that cycle.

Cryopreservation↗