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Biomedical subjects

P C Smith

Publications and source records attributed to P C Smith.

At least 19 recordsLinked to original sources
PubMed2006

Control of estradiol secretion in reproductive ageing.

BACKGROUND: Estradiol (E(2)) concentration is preserved in older reproductive-aged women despite a decrease in follicle number and androstenedione (AD) levels. We hypothesized that increased aromatase activity accounts for E(2) preservation in older women. METHODS: Older (36-46 years; n = 11) and younger (21-35 years; n = 10) women with 25- to 35-day menstrual cycles participated in a parallel design study. Daily blood samples were drawn starting at menses, and recombinant human FSH (rhFSH), 150 IU, was administered when the dominant follicle's diameter was > or =16 mm. FSH, LH, E(2), estrone (E(1)), AD and the AD/E(1) ratio were compared. RESULTS: E(2) and E(1) concentrations and the E(1)/E(2) ratio were similar across the follicular phase in older compared with younger women, whereas AD and the AD/E(1) ratio were lower. Older women had higher FSH concentrations in the early follicular phase and fewer small follicles. RhFSH-stimulated changes in E(1) were similar between older and younger subjects despite the smaller number of follicles. CONCLUSIONS: These findings suggest that E(2) secretion is maintained by increased aromatase function in older compared with younger reproductive-aged women, whereas there is no apparent difference in 17beta-hydroxysteroid dehydrogenase activity. The increased aromatase is probably driven by increased FSH in the early follicular phase and compensates for the decreased follicle number in older reproductive-aged women.

Adult↗
PubMed2006

Differential uPA expression by TGF-beta1 in gingival fibroblasts.

Transforming Growth Factor-beta1 (TGF-beta1) plays a key role in connective tissue remodeling and inflammation. Under pathological conditions, like periodontal disease, fibroblasts may display an altered response to this growth factor. To investigate this question, we have studied whether TGF-beta1 may differentially regulate the expression of urokinase at the protein level in primary cultures of fibroblasts derived from healthy gingiva, granulation tissue from gingival wounds, and chronic periodontal disease. We observed that TGF-beta1 may repress urokinase expression in healthy gingival fibroblasts and promote its production in granulation-tissue fibroblasts. A significant correlation was found between expression of the myofibroblast marker alpha-smooth-muscle actin and stimulation of urokinase production by TGF-beta1. Immunostaining of gingival wounds showed that myofibroblasts were involved in urokinase production. TGF-beta1-stimulated urokinase expression was blocked after inhibition of the c-jun-NH2 terminal kinase signaling pathway. We propose that stimulation of urokinase production by TGF-beta1 is involved in the responses of activated fibroblasts to tissue injury.

Actins↗
PubMed2005

Prolactin suppresses GnRH but not TSH secretion.

BACKGROUND/AIMS: In animal models, prolactin increases tuberoinfundibular dopamine turnover, which has been demonstrated to suppress both hypothalamic GnRH and pituitary TSH secretion. To test the hypothesis that prolactin suppresses GnRH and TSH secretion in women, as preliminary evidence that a short-feedback dopamine loop also operates in the human, the effect of hyperprolactinemia on GnRH and TSH secretion was examined. METHODS: Subjects (n=6) underwent blood sampling every 10 min in the follicular phase of a control cycle and during a 12-hour recombinant human prolactin (r-hPRL) infusion preceded by 7 days of twice-daily subcutaneous r-hPRL injections. LH and TSH pulse patterns and menstrual cycle parameters were measured. RESULTS: During the 7 days of r-hPRL administration, baseline prolactin increased from 16.0+/-3.0 to 101.6+/-11.6 microg/l, with a further increase to 253.7+/-27.7 microg/l during the 12-hour infusion. LH pulse frequency decreased (8.7+/-1.0 to 6.0+/-1.0 pulses/12 h; p<0.05) with r-hPRL administration, but there were no changes in LH pulse amplitude or mean LH levels. There were also no changes in TSH pulse frequency, mean or peak TSH. The decreased LH pulse frequency did not affect estradiol, inhibin A or B concentrations, or menstrual cycle length. CONCLUSION: These studies demonstrate that hyperprolactinemia suppresses pulsatile LH secretion but not TSH secretion and suggest that GnRH secretion is sensitive to hyperprolactinemia, but that TSH secretion is not. These data further suggest that the degree of GnRH disruption after 7 days of hyperprolactinemia is insufficient to disrupt menstrual cyclicity.

Adult↗
PubMed2005

Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part II. Anatomy.

OBJECTIVES: Duplex ultrasound investigation has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this paper was an initiative of the Union Internationale de Phlébologie (UIP), The aim was to obtain a consensus of international experts on the methodology to be used for assessment of anatomy of superficial and perforating veins in the lower limb by ultrasound imaging. DESIGN: Consensus conference leading to a consensus document. METHODS: The authors performed a systematic review of the published literature on duplex anatomy of the superficial and perforating veins of the lower limbs; afterwards they invited a group of experts from a wide range of countries to participate in this project. Electronic submissions from the authors and the experts (text and images) were made available to all participants via the UIP website. The authors prepared a draft document for discussion at the UIP Chapter meeting held in San Diego, USA in August 2003. Following this meeting a revised manuscript was circulated to all participants and further comments were received by the authors and included in subsequent versions of the manuscript. Eventually, all participants agreed the final version of the paper. RESULTS: The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination as well as the interpretation of images and measurements obtained. This document provides a detailed methodology for complete ultrasound assessment of the anatomy of the superficial and perforating veins in the lower limbs. CONCLUSIONS: The authors and a large group of experts have agreed a methodology for the investigation of the lower limbs venous system by duplex ultrasonography, with specific reference to the anatomy of the main superficial veins and perforators of the lower limbs in healthy and varicose subjects.

Chronic Disease↗
PubMed2004

Evidence of early ovarian aging in fragile X premutation carriers.

Up to 28% of female fragile X premutation carriers develop premature ovarian failure. To test the hypothesis that fragile X premutation carriers with ovulatory menstrual cycles exhibit hormone changes characteristic of early ovarian aging, 11 regularly cycling fragile X premutation carriers, 24-41 yr old (34.5 +/- 5.7 yr, mean +/- sd), drew daily blood samples across one menstrual cycle. LH, FSH, estradiol, progesterone (P4), inhibin A, and inhibin B levels were compared with levels in 22 age-matched, regularly cycling women, 23-41 yr old (34.6 +/- 5.8 yr), at each cycle stage. Total cycle (26.1 +/- 1.0 vs. 28.2 +/- 0.4 d; P < 0.05) and follicular phase length (12.9 +/- 0.8 vs. 14.5 +/- 0.4 d; P < 0.05) were decreased in fragile X premutation carriers compared with age-matched controls, whereas luteal phase length was similar (13.2 +/- 0.5 vs. 13.7 +/- 0.3 d; P = not significant). FSH was elevated across the follicular (21.9 +/- 3.5 vs. 11.2 +/- 0.5 IU/liter; P < 0.001) and luteal phases (14.6 +/- 3.9 vs. 7.9 +/- 0.5 IU/liter; P < 0.05) in fragile X premutation carriers compared with age-matched controls. Inhibin B in the follicular phase (77 +/- 11 vs. 104 +/- 6 pg/ml; P < 0.05) and inhibin A (3.4 +/- 0.7 vs. 5.8 +/- 0.5 IU/ml; P < 0.01) and P4 [7.3 +/- 1.0 vs. 10.1 +/- 0.7 ng/ml (23.2 +/- 3.0 vs. 32.1 +/- 2.3 nmol/liter); P < 0.05] in the luteal phase were decreased in fragile X premutation carriers compared with age-matched controls, whereas there was no difference in estradiol or LH. In summary, despite regular ovulatory cycles, FSH was increased in fragile X premutation carriers compared with age-matched controls. The increased FSH was accompanied by decreased inhibin B in the follicular phase and inhibin A and P4 in the luteal phase. These hormonal changes suggest that fragile X premutation carriers exhibit early ovarian aging despite regular menstrual cycles. Early ovarian aging in fragile X premutation carriers likely results from decreased follicle number and function, as reflected by lower inhibin B, inhibin A, and P4 levels.

Adult↗
PubMed2002

Measuring health system performance.

The improvement of health system performance has become a key policy issue in most developed nations. To that end, many initiatives to measure system performance are being put in place. This paper examines the performance measurement movement from a principal/agent viewpoint. It argues that the effectiveness of performance measurement systems depends on four key factors: the extent to which the chosen performance measures reflect faithfully the objectives of the system, the nature and quality of the data, the incentives for clinicians to scrutinize and act upon the data, and the culture of the organization within which the data are deployed. Although the optimal design of performance measurement systems depends heavily on local factors, they are likely to offer a highly cost-effective instrument for securing major improvements in system performance if properly deployed.

Editorial↗
PubMed2002

Higher risk of preterm birth and low birth weight in women with periodontal disease.

Pregnant women with periodontal disease (PD) may be at increased risk for having preterm low-birth-weight (PLBW) children. We investigated whether the maintenance of the mothers' periodontal health after 28 weeks' gestation reduces the risk of PLBW. Of the 639 women studied, 406 had gingivitis and received treatment before 28 weeks' gestation, and 233 had PD and were treated after delivery. Data about previous and current pregnancies and known risk factors were obtained from patients' medical records. Primary outcomes were delivery before 37 weeks' gestation or an infant with birth weight below 2500 g. The incidence of PLBW was 2.5% in periodontally healthy women, and 8.6% in women with PD (p = 0.0004, relative risk = 3.5, 95% CI, 1.7 to 7.3). Risk factors significantly associated with PLBW were previous PLBW, PD, fewer than 6 pre-natal visits, and low maternal weight gain. PD was associated with both preterm birth and low birth weight, independent of other risk factors.

Adolescent↗
PubMed2001

Determination of mycophenolic acid and its phenol glucuronide metabolite in human plasma and urine by high-performance liquid chromatography.

Simultaneous determination of mycophenolic acid (MPA) and mycophenolate phenol glucuronide (MPAG) in plasma and urine was accomplished by isocratic HPLC with UV detection. Plasma was simply deproteinated with acetonitrile and concentrated, whereas urine was diluted prior to analysis. Linearity was observed from 0.2 to 50 microg/ml for both MPA and MPAG in plasma and from 1 to 50 microg/ml of MPA and 5 to 2000 microg/ml MPAG in urine with extraction recovery from plasma greater than 70%. Detection limits using 0.25 ml plasma were 0.080 and 0.20 microg/ml for MPA and MPAG, respectively. The method is more rapid and simple than previous assays for MPA and MPAG in biological fluids from patients.

Chromatography, High Pressure Liquid↗
PubMed2001

Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice.

BACKGROUND: Despite clinical associations and in vitro data suggesting that autocrine interleukin-6 (IL-6) production contributes to prostate cancer progression or chemotherapy resistance, there have been no reports that explore the role of IL-6 on prostate tumors in vivo. In the present study, we investigated the effect of IL-6 inhibition on the growth of human prostate cancer xenografts in nude mice. METHODS: To determine if autocrine IL-6 production contributes to prostate cancer growth and chemotherapy resistance in vivo, xenografts of a human prostate cancer cell line that produces IL-6 (PC-3) were established in nude mice. The mice were randomly divided into four treatment groups: (1) saline (vehicle control) + murine IgG (isotype control); (2) etoposide + murine IgG; (3) saline + anti-IL-6 monoclonal antibody; and (4) etoposide + anti-IL-6 monoclonal antibody. Tumors were measured twice weekly during a 4-week treatment period. At the conclusion of the study, all mice were sacrificed, and in addition to final volume, tumors were evaluated for the degree of apoptosis by TUNEL analysis. RESULTS: Anti-IL-6 Ab (with saline or etoposide) induced tumor apoptosis and regression ( approximately 60% compared to initial tumor size). Etoposide alone did not induce tumor regression or apoptosis in this animal model, and there was no synergy between anti-IL-6 Ab and etoposide. CONCLUSIONS: These studies suggest that IL-6 contributes to prostate cancer growth in vivo, and that targeting IL-6 may contribute to prostate cancer therapy.

Animals↗
PubMed2001

Interleukin-6 and prostate cancer progression.

Prostate cancer, while initially dependent on androgens for proliferation, progresses to an androgen-independent state. Evidence has been accumulating that interleukin-6 (IL-6) may contribute to prostate cancer progression. Serum levels of IL-6 correlate with prostate tumor burden and patient morbidity. The prostate tissue itself appears to be a source of IL-6 and its receptor. Furthermore, experimental data suggest that IL-6 is an autocrine and paracrine growth factor for androgen-independent prostate cancer cell lines. For example, inhibition of IL-6, with anti-IL-6 antibody, sensitizes androgen-independent prostate cancer cells to chemotherapeutic agents in vitro. Finally, IL-6 activates a variety of signal transduction cascades, some which stimulate androgen receptor activity, in prostate cancer cells. These data suggest that targeting IL-6 may have multiple benefits in prostate cancer patients.

Animals↗
PubMed2001

Prostate carcinoma skeletal metastases: cross-talk between tumor and bone.

The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.

Animals↗
PubMed2001

Whole blood microvolume laser scanning cytometry for monitoring resting and activated platelets.

Enumerating and phenotyping of platelets, resting and activated, from whole blood is important for both the identification and verification of many disease states. Microvolume laser scanning cytometry (MLSC) has been shown to be a simple method for enumerating and phenotyping peripheral blood cells. Here, the utility of MLSC, in conjunction with an anticoagulant containing platelet activation inhibitors, for simultaneously measuring platelet count, phenotype and responsiveness directly from non-fixed whole blood was examined. CTAD or EDTA anticoagulated blood was collected from five to 20 healthy volunteers, stained with fluorescence-labeled antibodies specific for platelet antigens, and run on an in-house modified MSLC device. MLSC was able to measure antigens CD9, CD29, CD36, CD41, CD42a, CD42b, and CD61 on platelets and determine an average of 2.3 x 10(5) +/- 7 x 10(4) platelets per microliter. Counts correlated well with those obtained from the Cell-Dyn 3500 (r(2)=0.84). Agreeing with previous data, less than 2% of platelets from peripheral blood of normal individuals expressed the activation markers CD62P or CD63. After in vitro thrombin activation, >93% of the platelets expressed activation markers. Data presented here shows the benefits of using MLSC in combination with platelet inhibitors to quantitate and phenotype platelets while maintaining a viable responsive state.

Anticoagulants↗
PubMed2001

Capitation and risk adjustment in health care financing: an international progress report.

In every system of health care, capitation payments have become the accepted tool used by health care purchasers in much of the developed world to determine prospective budgets. The policy prescription of capitation is perceived to address both equity objectives (of great importance in publicly funded systems of health care) and efficiency objectives (the dominant concern in competitive insurance markets). An examination of the current state of the art in 20 countries outside the United States in which health care capitation has been implemented confirms that capitation has assumed central importance within diverse systems of health care. In practice, however, the setting of capitation payments has been heavily constrained to date by poor data availability and unsatisfactory analytic methodology.

Australia↗
PubMed2001

Ethics and geographical equity in health care.

Important variations in access to health care and health outcomes are associated with geography, giving rise to profound ethical concerns. This paper discusses the consequences of such concerns for the allocation of health care finance to geographical regions. Specifically, it examines the ethical drivers underlying capitation systems, which have become the principal method of allocating health care finance to regions in most countries. Although most capitation systems are based on empirical models of health care expenditure, there is much debate about which needs factors to include in (or exclude from) such models. This concern with legitimate and illegitimate drivers of health care expenditure reflects the ethical concerns underlying the geographical distribution of health care finance.

Delivery of Health Care↗
PubMed2000

Equity in the allocation of health care resources.

This paper examines some of the issues that arise when seeking to tackle health inequalities in a context of limited health care resources. Increasingly, central agencies are using devolved budgets for health care providers as a central instrument of expenditure control. Equity objectives play an important role in the resource allocation methods used to determine such budgets. Yet, unless integrated into a proper system of risk management, the use of budgets can lead to serious inequity. The paper discusses the potential contributions of different disciplines to promoting equity within a health care budgetary regime.

Budgets↗