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Biomedical subjects

P Stratton

Publications and source records attributed to P Stratton.

At least 19 recordsLinked to original sources

Convectively driven polymerase chain reaction thermal cycler.

We have fabricated a low-cost disposable polymerase chain reaction thermal chamber that uses buoyancy forces to move the sample solution between the different temperatures necessary for amplification. Three-dimensional, unsteady finite element modeling and a simpler 1-D steady-state model are used together with digital particle image velocimetry data to characterize the flow within the device. Biological samples have been amplified using this novel thermal chamber. Time for amplification is less than 30 min. More importantly, an analysis of the energy consumption shows significant improvements over current technology.

Electric Power Supplies↗

Causal attributions in delusional thinking: an investigation using qualitative methods.

OBJECTIVES: To investigate the attributions offered spontaneously during interview by patients who have delusional beliefs. Specifically, to assess whether people with delusional beliefs reason in a way that is analysable. If so, to extend the findings from previous research to provide a detailed picture of the patients' accounts that could inform cognitive therapies for psychosis. METHOD: A group of 31 patients with delusional beliefs were interviewed using a semi-structured open-ended interview. Their causal attributions were identified and analysed in terms of standard definitions of attributional theory using the Leeds Attributional Coding System. RESULTS: Patients made an average of 96 attributions each. These showed a high degree of recognizable coherence in reasoning, including when directly discussing delusional beliefs. The patterns of attributing were partly consistent with previous research findings, with external attributions being offered for negative events. Several other aspects emerged, indicating a pervasive negativity, with non-delusional aspects of the illness being a major concern. When delusions were described as a cause of events, the dominant pattern of attributing was stable, internal, personal and uncontrollable, with negative outcomes. When delusions were reported as an outcome, the patient was more in control. CONCLUSIONS: The reasoning processes of patients with delusional beliefs are in many aspects normal and include patterns not identified by the ASQ. Attributing in relation to delusions differs from talk about other subjects. The qualitative attributional approach provided a detailed and rich picture of the world of these patients. Interpretable tendencies are described that should provide information useful to those practising and evaluating cognitive therapies.

Adult↗

High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.

BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.

Adolescent↗

A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women.

Previous studies in women have shown that the antiprogestin mifepristone delays or inhibits folliculogenesis. The purpose of this study was to explore whether a new analogue, CDB-2914, has similar effects on folliculogenesis, ovulation, or on subsequent luteal phase endometrial maturation. Forty-four normally cycling, healthy women recorded urine LH and vaginal bleeding during pre-treatment, treatment, and post-treatment cycles. At a lead follicle diameter of 14-16 mm, a single oral dose (10, 50, 100 mg) of CDB-2914 or placebo was given, and daily ultrasound, oestradiol and progesterone were obtained until follicular collapse; an endometrial biopsy was obtained 5-7 days later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB-2914 suppressed lead follicle growth, causing a dose-dependent delay in folliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicles were observed at the 100 mg dose, all women had follicular collapse. There was a significant delay in endometrial maturation after CDB-2914 at all doses. The treatment cycle was lengthened by 1-2 weeks in 30% at 100, 27% at 50 and 9% at 10 mg. CDB-2914 altered ovarian and endometrial physiology without major effects on menstrual cyclicity and may have therapeutic utility.

Adolescent↗

Cervical dysplasia on cervicovaginal Papanicolaou smear among HIV-1-infected pregnant and nonpregnant women. Women and Infants Transmission Study.

OBJECTIVE: To assess the association of squamous intraepithelial lesions (SIL) on cervicovaginal Papanicolaou (Pap) smear among women infected with HIV-1 and their pregnancy status, and historical and clinical factors. METHODS: Study enrollment Pap smears of 452 pregnant and 126 nonpregnant HIV-infected women had cytologic evaluation. The rates of SIL were compared with pregnancy status, immunosuppression, presence of sexually transmitted diseases (STDs) and demographic features. RESULTS: Rates of low grade SIL were similar for pregnant and nonpregnant HIV-1-infected women (17% and 23.8%, respectively; p = .09). Of them, 12 women, 9 pregnant and 3 nonpregnant, had high grade SIL. None had invasive cervical cancer. Low CD4 percentage (odds ratio, [OR] = 3.8; 95% confidence interval [CI], 2.0-7.3) and inflammation (OR = 2.8; 95% CI, 1.8-4.3) were associated with SIL. An association between herpes simplex and SIL (OR = 3.3; 95% CI, 1.1-9.5) was less certain due to clinical diagnosis and low prevalence of herpes simplex (17 of 456 women). CONCLUSIONS: Pap smears for a cohort of HIV-infected pregnant and nonpregnant women revealed a high prevalence of LGSIL but a low prevalence of HGSIL and no cases of cervical cancer. Although pregnancy may not affect the rate of Pap smear abnormalities, SIL is associated with immunosuppression, cervical inflammation, and herpes simplex. Closer surveillance of HIV-1-infected women with these risk factors may be warranted.

Adolescent↗

Obstetric and newborn outcomes in a cohort of HIV-infected pregnant women: a report of the women and infants transmission study.

OBJECTIVE: To determine obstetric and neonatal outcomes in a cohort of HIV-infected pregnant women and to assess whether HIV-related immunosuppression increases the risk of adverse outcomes of pregnancy. METHODS: Between 1989 and 1994, interview, physical examination, laboratory, and medical record data were prospectively collected from HIV-infected pregnant women and on their newborns. Factors associated with adverse pregnancy outcome and HIV disease status were correlated with pregnancy outcome using logistic regression analysis. RESULTS: 634 women delivered after 24 weeks of gestation. Preterm birth, low birth weight, and small-for-gestational-age neonates occurred in 20.5%, 18.9%, and 24.0% of pregnancies, respectively. Factors associated with low birth weight were CD4 percentage <14%, history of adverse pregnancy outcome, pediatric HIV infection, bleeding during pregnancy, and Trichomonas infection. Preterm birth was associated with CD4 percentage <14%, a history of adverse pregnancy outcome, and bleeding during pregnancy. Being small for gestational age was associated with maternal hard drug use during pregnancy, Trichomonas infection, history of adverse pregnancy outcome, and hypertension. CONCLUSIONS: Adverse pregnancy outcomes are common for HIV-infected women and are associated with low maternal CD4 percentage and pediatric HIV infection. Preterm birth, low birth weight, and small-for-gestational-age ranking, however, are also associated with previously recognized sociodemographic and obstetric factors that are not unique to HIV infection.

Adult↗

Families: accounts of the causal processes in food choice.

Much of the previous research into the processes involved in food choice has made use of methodologies that neglect the social and familial context in which such decisions are made. The study reported here used a different approach to gather qualitative data from family members regarding their decision processes in the form of naturally expressed social explanations or attributions. Interviews were conducted with 149 family members from a total of 83 British families from four locations. The participants were encouraged to discuss their own personal experience of food choice, including their dietary decisions and behaviours and the factors involved in the process, using systemic interviewing techniques. The 52 h of interview material obtained were subjected to attributional analysis using the Leeds Attributional Coding System (LACS), a qualitative research tool designed for work with families. The data, in the form of 7062 fully coded belief statements or attributions, provided some preliminary observations of the way that families understand and socially explain their food-based decisions. The approach offers a different perspective on family food choice to those provided through more traditional experimental research and surveys.

Adult↗

A miniature analytical instrument for nucleic acids based on micromachined silicon reaction chambers.

In this paper, we describe a miniature analytical thermal cycling instrument (MATCI) to amplify and detect DNA via the polymerase chain reaction in real-time. The MATCI is an integrated, miniaturized analytical system that uses silicon-based, high-efficiency reaction chambers with integrated heaters and simple, inexpensive electronics to precisely control the reaction temperatures. Optical windows in the silicon and solid-state, diode-based detection components are employed to perform real-time fluorescence monitoring of product DNA production. The entire system fits into a briefcase and runs on rechargeable batteries. The applications of this miniaturized nucleic acid analysis system include clinical, research, environmental, and agricultural analyses as well as others which require rapid, portable, and accurate analysis of biological samples for nucleic acids. This paper describes the MATCI and presents results from ultrafast thermal cycling and real-time PCR detection. Examples include human genes and pathogenic viruses and bacteria.

Actins↗

HIV quantitation in spiked vaginocervical secretions: lack of non-specific inhibitory factors. DATRI 005 Study Team. Division of AIDS Treatment Research Initiative.

The objective of this study was to assess the effect of menstrual phase on the ability to quantitate HIV-1 in vaginocervical secretions (VCS) through reconstruction experiments with HIV seronegative VCS collected throughout the menstrual cycle. Measurement of HIV-1 inoculated into both fresh and frozen VCS was undertaken by quantitative micro co-culture, p24 antigen assay and polymerase chain reaction (PCR) for both HIV-1 RNA and pro-viral DNA. Two laboratories carried out these assays over a range of viral concentrations. The study involved a randomized factorial design and the factors were: (1) diluents (phases of the menstrual cycle and controls); (2) laboratories; (3) stock concentrations; and (4) frozen versus fresh VCS samples. Each assay was assessed independently using a random effects analysis of variance (ANOVA) model. No statistical differences due to menstrual cycle were seen in the assay results of p24 antigen (P = 0.08), PBMC culture (P = 0.74), plasma culture (P = 0.13), cell-free RNA (P = 0.44), cell-associated RNA (P = 0.58) and cell-associated DNA (P = 0.43). Inter-laboratory differences were statistically significant for cell-free RNA (P < 0.001), cell-associated DNA (P < 0.001) and p24 (P < 0.001). It is concluded that VCS obtained throughout the menstrual cycle from HIV-uninfected women lacks intrinsic inhibitory factors which could limit detection and quantification by antigen, culture or nucleic acid-based technologies for HIV-1 in VCS throughout the menstrual cycle. Using a standardized collection procedure, we suggest that variation in HIV quantity over time, when reported in VCS of infected women, should be attributed to HIV-associated biologic factors, rather than non-specific or other technical factors.

Analysis of Variance↗

Rapid pathogen detection using a microchip PCR array instrument.

An array of PCR microchips for rapid, parallel testing of samples for pathogenic microbes is described. The instrument, called the Advanced Nucleic Acid Analyzer (ANAA), utilizes 10 silicon reaction chambers with thin-film resistive heaters and solid-state optics. Features of the system include efficient heating and real-time monitoring, low power requirements for battery operation, and no moving parts for reliability and ruggedness. We analyzed cultures of Erwinia herbicola vegetative cells, Bacillus subtilis spores, and MS2 virions, which simulated pathogenic microbes such as Yersinia pestis, Bacillus anthracis spores, and Venezuelan equine encephalitis, respectively. Detection of microbes was achieved in as little as 16 min with detection limits of 10(5)-10(7) organisms/L (10(2)-10(4) organisms/mL).

Bacillus subtilis↗

Quantitation of vaginally administered nonoxynol-9 in premenopausal women.

A feasibility study was performed in 11 healthy nonpregnant premenopausal women to determine a method for collection and recovery of vaginally administered nonoxynol-9. We also determined if nonoxynol-9 could be quantitated in vaginal lavage fluid obtained 2 h after instillation of a standard precoitol dose of a foam formulation of nonoxynol-9. Samples were analyzed in batch using a validated normal phase high-performance liquid chromatography (HPLC) method. Two hours after instillation of one dose of Delfen Contraceptive Foam (100 mg), the quantity of nonoxynol-9 collected ranged from 10.8 to 67.8 mg (mean: 35.4 mg). This corresponds to a recovery of 11.70%, of the administered dose. Quantitation of vaginally administered nonoxynol-9 is both practical and feasible. These data represent a critical first step in the evaluation of the safety and effectiveness of nonoxynol-9-containing products in the prevention of sexually transmitted diseases.

Administration, Intravaginal↗

Using spoken attributions to classify abusive families.

Despite claims that beliefs held by abusive parents are important indicators of family functioning, few studies have explored the relationship between patterns of beliefs and severity of abuse. This study applies findings from marital research that demonstrate that maladaptive attributional patterns predict the level of distress experienced in adult relationships. It examines spoken attributions produced by 18 families during diagnostic therapy sessions following serious abuse of a child. Attributions were identified from transcripts and coded using a standard system. Patterns of attributions, defined on the basis of previous work, successfully predicted classification of families by therapists as Good, Uncertain, and Poor, in terms of prognosis for rehabilitation. Using this classification to test hypotheses based on attributional style, group differences were found. In families rated Good, parents were more likely to attribute more control to self than child for negative outcomes. They were also more likely to nominate themselves as causing negative events. Case accounts of families from each category are presented to illustrate how attributional analysis can contribute to an understanding of the individual nature of child abuse.

Adult↗

Chromatographic methods for quantitative analysis of native, denatured, and aggregated basic fibroblast growth factor in solution formulations.

High-performance liquid chromatography (HPLC) methods were developed for evaluating stability of human recombinant basic fibroblast growth factor (bFGF) against denaturation and aggregation in solution formulations. Reversed-phase chromatography (RP-HPLC)-insensitive to bFGF tertiary structure--was used to measure total soluble protein; heparin affinity chromatography (HepTSK) provided quantitative analysis of native bFGF species. The folding state of bFGF was determined by fluorescence spectroscopy: Tryptophan emission, which was quenched in native protein, increased upon unfolding. Slow unfolding/refolding kinetics of bFGF in 2 M guanidine hydrochloride made possible the separation of native from denatured species by size exclusion chromatography (SEC). Although the tertiary structure affected bFGF retention times, it did not change the sample recovery by SEC. These chromatographic techniques, which quantitatively measure physical and chemical changes taking place in solution formulations, can be used in future investigations of bFGF stability.

Chemical Phenomena↗

Major degradation products of basic fibroblast growth factor: detection of succinimide and iso-aspartate in place of aspartate.

The degradation products of basic fibroblast growth factor (bFGF) were isolated by ion exchange HPLC (HP-IEC) and characterized. The predominant product at pH 5 was a succinimide in place of aspartate15 as determined by LC/MS, N-terminal sequencing, and susceptibility to degradation at pH > 6.5. The rate of appearance of the succinimidyl-bFGF at 22 degrees C was comparable to that reported for small peptides, consistent with a high flexibility predicted for asp15-gly. Tryptic mapping together with [3H]-methylation indicated that iso-aspartate was formed at the position of asp15. Size exclusion HPLC indicated the presence of intact and truncated dimers and trimers which associated through disulfide linkages. Two truncated monomer forms were found that co-eluted by HP-IEC; the cleavages were determined to be at asp28-pro and asp15-gly using LC/MS and N-terminal sequencing. These degradation products which occurred at sites that are away from receptor or heparin binding domains of bFGF remained bioactive in a cell proliferation assay.

Amino Acid Sequence↗

A randomised trial of routine versus selective counselling in perinatal bereavement from congenital disease.

OBJECTIVE: To find out whether routine counselling improves psychological wellbeing after bereavement for fetal abnormality. DESIGN: A randomised trial among bereaved couples who did not demonstrate any unexpected strain or psychopathology after bereavement. SETTING: St. James's University Hospital, Leeds. SUBJECTS: Fifty-seven couples. INTERVENTIONS: Independent counselling by an experienced psychotherapist. MAIN OUTCOME MEASURES: Self-administered questionnaires measuring grief, anxiety and depression and a structured psychological interview 16 to 20 months after the loss. Anniversaries of a death or expected birth date were avoided. RESULTS: There were no differences in outcome between women randomised to the study group or randomised to the control group with respect to grief, anxiety, depression or the results of the structured overview. Among those in the randomised study group, women who attended for counselling had a much better outcome than women who defaulted from counselling. Overall, women who underwent termination of pregnancy did slightly worse than those who had experienced stillbirth or neonatal death. On an informal basis, the clinician concerned believes that he was better able to help bereaved couples as a result of feedback and criticism from the independent counsellor. CONCLUSIONS: (1) The hypothesis that all couples should have independent counselling after prenatal loss for congenital abnormality is unproven, but it is likely that clinicians can benefit from feedback from a counsellor; (2) it is possible that termination of pregnancy is more psychopathogenic than other forms of fetal loss; (3) people who attend for their counselling sessions are probably inherently better able to adjust to bereavement; (4) trials of psychological intervention are feasible, but follow up is either difficult to achieve or expensive.

Abortion, Spontaneous↗

The stability of bFGF against thermal denaturation.

The influence of sulphated ligand and pH on thermal denaturation of basic fibroblast growth factor (bFGF) was investigated by differential scanning calorimetry (DSC), and verified by fluorescence spectrophotometry. Purity of bFGF before and after heat denaturation was assessed by SDS-PAGE analysis. In DSC studies the samples were heated to 95 degrees C. The midpoint of the temperature change in the thermogram was designated as Tm. Sulphated ligand experiments were undertaken in potassium phosphate (pH 6.5) and sodium acetate buffers. Control thermograms (with no ligand) showed a Tm at 59 degrees C in potassium phosphate buffer. Higher Tm values were noted as sulphated ligand concentration was increased. Similarly when heparin was added, the Tm moved to a higher temperature. A ratio as low as 0.3:1 of heparin to bFGF, increased the Tm to 90 degrees C, which is a 31 degrees C shift in Tm. The effect of pH on thermal denaturation of bFGF was studied in a citrate-phosphate-borate buffer system. A shift in Tm from 46 to 65 degrees C was observed as the pH is changed from 4 to 8. Changes in protein conformation as a function of pH were monitored by fluorescence spectroscopy. It was found that a pH range from 5 to 9 is optimal for the stability of bFGF formulations. In a stability study it was noted that heparin protected bFGF from thermal denaturation only at high temperature.

Buffers↗