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Biomedical subjects

J Piper

Publications and source records attributed to J Piper.

At least 19 recordsLinked to original sources
PubMed2006

The insulin sensitiser pioglitazone does not influence skin microcirculatory function in patients with type 2 diabetes treated with insulin.

AIMS/HYPOTHESIS: Insulin resistance is associated with abnormal microvascular function. Treatment with insulin sensitisers may provoke oedema, suggesting microvascular effects. The mechanisms underlying the peripheral oedema observed during glucose-lowering treatment with thiazolidinediones are unclear. Therefore we examined the effect of pioglitazone on microvascular variables involved in oedema formation. METHODS: Subjects (40-80 years) with type 2 diabetes and on insulin were randomised to 9 weeks of pioglitazone therapy (30 mg/day; n=14) or placebo (n=15). The following assessments were performed at baseline and 9 weeks: microvascular filtration capacity; isovolumetric venous pressure; capillary pressure; capillary recruitment following venous or arterial occlusion; postural vasoconstriction; and maximum blood flow. A number of haematological variables were also measured including vascular endothelium growth factor (VEGF), IL-6 and C-reactive protein (CRP). RESULTS: Pioglitazone did not significantly influence any microcirculatory variable as compared with placebo (analysis of covariance [ANCOVA] for microvascular filtration capacity for the two groups, p=0.26). Mean VEGF increased with pioglitazone (61.1 pg/ml), but not significantly more than placebo (9.76 pg/ml, p=0.94). HbA(1c) levels and the inflammatory markers IL-6 and CRP decreased with pioglitazone compared with placebo (ANCOVA: p=0.009, p=0.001 and p=0.004, respectively). CONCLUSIONS/INTERPRETATION: Pioglitazone improved glycaemic control and inflammatory markers over 9 weeks but had no effect on microcirculatory variables associated with oedema or insulin resistance in type 2 diabetic patients treated with insulin.

Adult↗
PubMed2004

Managing genital infection in community family planning clinics: an alternative approach to holistic sexual health service provision.

OBJECTIVE: To pilot and evaluate sexually transmitted infection (STI) management in community family planning clinics (FPCs). METHODS: Number of STI tests taken, positive results, infections treated, contacts traced/treated, referrals to specialist services and time from testing to treatment were documented as well as age and sex of the population tested. RESULTS: STI tests taken increased from 233 to 308/month and male clients seen increased from 114 to 147/month across all clinics. Chlamydia prevalence rates in one large clinic increased from 6.7% to 11.9%. 82% of those with STIs in this clinic were treated. Of 44 clients treated for chlamydia, 84% had partner notification performed, 0.43 contacts were treated for every client with chlamydia and referrals to specialist services decreased. 70% of STIs were detected in clinic users under the age of 25 and 45.5% of clients tested under the age of 16 had an STI. Before STI treatment was available at FP clinics 52% of clients with STIs attended specialist services after referral and time from testing to treatment was 19 days. Managing STIs in the community increased treatment rates to 82% with a testing to treatment time of 10 days. CONCLUSIONS: The management of uncomplicated genital infection in community FPCs working in partnership with specialist services is a feasible and effective approach to holistic sexual health service provision.

Adult↗
PubMed2003

Autoantibodies of patients with coeliac disease are insufficient to block tissue transglutaminase activity.

BACKGROUND AND AIMS: Coeliac disease (CD) is characterised by the presence of autoantibodies against tissue transglutaminase (tTG), the endomysial autoantigen. This study was performed to determine the effect of purified autoantibodies on the enzymatic activity of tTG. METHODS: Total IgA and IgG class antibodies and purified anti-tTG autoantibodies were isolated from sera of untreated patients with CD and controls. The inhibitory capacity of the antibodies on tTG activity was checked by a fluorometric assay based on the incorporation of monodansyl cadaverine into casein and by tTG-catalysed cross linking of biotinylated cadaverine to gliadin. RESULTS: The enriched IgA and IgG fractions of five patients with CD and three controls resulted in no significantly different inhibition of enzymatic activity. In contrast, the use of affinity purified anti-tTG autoantibodies of 12 patients with CD led to a dose dependent reduction of tTG activity, compared to control immunoglobulins (n=6). However, the remaining activity was sufficient for cross linking of cadaverine into gliadin, and enzymatic tTG activity was only blocked completely by high concentrations of a monoclonal antibody, which is directed to the active centre of tTG. CONCLUSIONS: Despite a partial inhibitory effect of isolated anti-tTG autoantibodies from patients with CD, residual enzymatic activity remains sufficiently high to cast doubt on their in vivo relevance.

Animals↗
PubMed2002

Comparative analysis of comparative genomic hybridization microarray technologies: report of a workshop sponsored by the Wellcome Trust.

BACKGROUND: Array-comparative genomic hybridization (CGH), although providing much higher resolution compared with conventional CGH, has not yet become a widely applied method for the analysis of genomic gains and losses. METHODS: In January 2002, the Wellcome Trust sponsored a workshop where many of the laboratories developing this technology met to compare different methodologies for array-CGH. Fourteen groups participated, comprising 11 from Europe and 3 from the United States. To facilitate objective analysis, each laboratory constructed arrays using the same anonymous clones and performed a series of test hybridizations using identical genomic DNAs. RESULTS: A figure of merit (FM) was developed to summarize entire collections of data from each laboratory in a single measurement. The FMs consistently showed that a few groups produced quantitative array hybridization data of high quality, whereas a majority achieved a lower standard. CONCLUSIONS: The conclusions of the workshop were that polymerase chain reaction-based methods for the amplification of large insert clones for arraying were effective for array-CGH. It was also concluded that hybridizations performed under coverslips or in automated hybridization apparatus were less effective than hybridizations performed in simple wells with gentle rocking. A common experience by the participants was the batch-to-batch variability of commercial Cot1 preparations in their ability to suppress hybridization to repeat sequences. (Supplementary material for this article can be found in the online issue, which is available at http://www.interscience.wiley.com/jpages/0196-4763/suppmat/49_2/v49.43.html or at http://www.sanger.ac.uk/HGP/Cytogenetics/Publications/Cytometry Sept 2002/Supplemental.pdf.)

Animals↗
PubMed2001

Minority women with sexually transmitted diseases: sexual abuse and risk for pelvic inflammatory disease.

Mexican American and African American women (N = 617) with a sexually transmitted disease (STD) underwent a targeted physical exam and questioning regarding sexual abuse, current genitourinary symptomatology, and pelvic inflammatory disease (PID) risk behaviors to determine the relationship between sexual abuse and risk for PID. Sexually abused women (n = 194) reported higher PID risk behaviors, including earlier coitus, more sex partners, higher STD recurrence, and a tendency toward delayed health-seeking behavior. They also reported more severe genitourinary symptomatology, confirmed by physical exam, and presumptive diagnoses of PID. These characteristics identify sexually abused women at high risk for PID. Because of its considerable impact on risk for PID, assessment for sexual abuse is essential in clinical management of women with STD and for diagnosis of PID.

Adolescent↗
PubMed2001

Sexual abuse and sexual risk behaviors of minority women with sexually transmitted diseases.

The relationship between sexual abuse and sexually transmitted disease (STD) represents an important and underinvestigated context of domestic violence. This study examined the association between sexual abuse, sexual risk behaviors, and risk for reinfection and HIV among minority women with STD. Mexican American and African American women (n = 617) with active STD entered a randomized study of behavioral intervention to reduce STD recurrence. Each underwent questioning at entry regarding sexual abuse and sexual risk behaviors. Comparisons of these behaviors using chi-square, t tests, and logistic regression were made by history of sexual abuse. Sexually abused women were more likely to have lower incomes, earlier coitus, STD history, currently abusive partners, new sex partners, anal sex, and bleeding with sex, placing them at increased risk for STD reinfection and HIV. Due to this association with sexual risk behavior, assessment for sexual abuse is essential in programs focusing on STD/HIV prevention.

Adult↗
PubMed2000

Classification accuracy in multiple color fluorescence imaging microscopy.

BACKGROUND: The discriminatory power and imaging efficiency of different multicolor FISH (M-FISH) analysis systems are key factors in obtaining accurate and reproducible classification results. In a recent paper, Garini et al. put forth an analytical technique to quantify the discriminatory power ("S/N ratio") and imaging efficiency ('excitation efficiency') of multicolor fluorescent karyotyping systems. METHODS: A parametric model of multicolor fluorescence microscopy, based on the Beer-Lambert law, is analyzed and reduced to a simple expression for S/N ratio. Parameters for individual system configurations are then plugged into the model for comparison purposes. RESULTS: We found that several invalid assumptions, which are used to reduce the complex mathematics of the Beer-Lambert law to a simple S/N ratio, result in some completely misleading conclusions about classification accuracy. The authors omit the most significant noise source, and consider only one highly abstract and unrepresentative situation. Unwisely chosen parameters used in the examples lead to predictions that are not consistent with actual results. CONCLUSIONS: The earlier paper presents an inaccurate view of the M-FISH situation. In this short communication, we point out several inaccurate assumptions in the mathematical development of Garini et al. and the poor choices of parameters in their examples. We show results obtained with different imaging systems that indicate that reliable and comparable results are obtained if the metaphase samples are well-hybridized. We also conclude that so-called biochemical noise, not photon noise, is the primary factor that limits pixel classification accuracy, given reasonable exposure times.

Chromosomes↗
PubMed2000

Fluorescence staining and flow cytometry for monitoring microbial cells.

Large numbers of microbiological samples are analysed annually using traditional culture-based techniques. These techniques take hours to days to yield a result, are tedious and are not suitable for non-culturable microorganisms. Further, culture-based techniques do not provide real-time information on the physiological status of the organism in situ which is important in the industrial manufacture of many microbial products. Flow cytometry offers the prospect of real-time microbial analysis of individual microorganisms, without dependency on microbial culture. However, flow cytometry has not been extensively used as a tool for routine microbial analysis. This has been mainly due to the high cost and complexity of instrumentation, the need for trained flow cytometrists and the lack of assay kits with appropriate biological reagents for specific applications. Many modern instruments are now relatively simple to operate, due to improvements in the user-interface, and no longer need a specialist operator. However, most cytometers are still reliant on analogue technology first developed 20-30 years ago. The incorporation of modern, solid state opto-electronics combined with micro-fabrication and digital signal processing technology offers the prospect of simple to use, low cost and robust instruments suitable for microbial analyses. Advances are being made in the development of a range of biological reagents and these are now being formulated into simple to use kits for microbiological applications. Currently, these kits are largely restricted to simple analyses, for example to assay for total or viable numbers of microorganisms present. However, technologies are available to selectively label specific types of microorganisms. For example, fluorescent antibodies can be used to label microorganisms according to expression of particular antigens, fluorescent in situ hybridisation to label according to phylogeny and fluorogenic enzymatic substrates to label according to expression of specific enzyme activities. Reagents are also available that stain viruses sufficiently brightly to enable their direct detection in environments such as sea water. Microorganisms need to be detected in a variety of different matrices (e.g., water, mud, food, and beverages) and these matrices may be highly variable in nature (e.g., tap water compared to river water). Many matrices have high background autofluorescence (e.g., algae and minerals in water samples) or may bind non-specifically to the fluorescent biological reagents used (e.g., protein micelles in milk). Formulation of biological reagents and sample pre-treatments are critical to the development of suitable microbiological assays. Here, developments in instrumentation and biological reagents for microbiological applications are reviewed with specific examples from environmental or industrial microbiology. The broader considerations for the development of microbial assays for flow cytometry are also considered.

Animals↗
PubMed2000

The role of fluorescence in situ hybridization technologies in molecular diagnostics and disease management.

Large genomic changes, such as aneuploidy, deletions, and other chromosomal rearrangements, have long been associated with pregnancy loss, congenital abnormalities, and malignancy. These genomic changes are quantitative, unambiguous, and fundamental in the transition of normal cells to abnormal ones. Detection of these large genetic changes has an increasingly important role in determining patient diagnosis and care, including therapeutic selection. We have developed two major product platforms that assess genomic changes at various levels of resolution. Fluorescence in situ hybridization (FISH) techniques and the related technology of array-based comparative genomic hybridization (CGH) allow detection of genesized or larger alterations in the genome. FISH is a robust DNA probe technology that can measure both balanced and unbalanced genomic changes on a cell-by-cell basis. In most instances, it is not dependent on metaphase chromosomes, and it is widely used in clinical diagnostics. Array-based CGH has much greater multiplexing capabilities than FISH. This technology has the potential to examine many regions of the genome simultaneously for changes in DNA copy number and identify complex patterns of gains and losses within the genome. In this article, we review several of the current medical applications of FISH and discuss such advanced techniques as CGH and array-based CGH.

Databases, Factual↗
PubMed2000

Epidemiology of human herpesvirus 6 (HHV-6) infection in pregnant and nonpregnant women.

BACKGROUND: Human herpesvirus 6 (HHV-6) is a ubiquitous virus primarily associated with benign conditions such as febrile syndromes and exanthem subitum (roseola infantum). Sexual, horizontal, and vertical transmission have been suggested. Little information is available regarding HHV-6 infection in women of reproductive age. OBJECTIVE: Describe epidemiology of HHV-6 infection in pregnant and nonpregnant women. STUDY DESIGN: The study sample consisted of 569 women, age 18-45, who attended a university family planning clinic (nonpregnant, n=224) and two obstetrics clinics (pregnant [first trimester], n=345) in San Antonio, TX between October 1995 and May 1998. Blood and a vaginal swab, as well as sociodemographic information, were collected from each participant. Plasma was tested for HHV-6 IgG antibodies using a standard immunofluorescence assay (IFA). Lysed material from vaginal swabs was tested for HHV-6 DNA by polymerase chain reaction (PCR). Products were screened by enzyme-linked immunosorbent assay and positive tests were confirmed by repeat PCR followed by Southern analysis. PCR-positive samples were subtyped using an established method. RESULTS: All subjects were HHV-6 antibody positive. Geometric mean titers of HHV-6 antibodies were significantly higher among nonpregnant versus pregnant women. Moreover, a higher proportion of nonpregnant versus pregnant women had antibody titers >/=160 and >/=320. This association persisted even after adjusting for a number of sociodemographic and clinical factors. Low rates of HHV-6 shedding in the genital tract were observed for both groups (pregnant, 7/297 [2.0%]; nonpregnant, 8/214 [3.7%]). Of 14 samples subtyped, four (29%) were subtype A. CONCLUSION: The present study showed that 100% of the study sample was infected with HHV-6. Higher HHV-6 antibody titers, however, were noted in nonpregnant women. Both groups shed virus at low rates in the genital tract. HHV-6 subtype A was identified more commonly than previously reported. Further longitudinal studies are required to assess the consequences of maternal HHV-6 infection.

Adolescent↗
PubMed2000

Comparing three patient-controlled analgesia methods.

Among 301 patients randomly assigned to use one of three methods for patient-controlled analgesia (PCA), no statistically significant differences were found for self-reported pain or acceptability of PCA method. Methods yielded differences in on-demand bolus analgesia use and number of symptoms.

Analgesia, Patient-Controlled↗
PubMed1999

Inhibitors of poly (ADP-ribose) synthetase protect rat cardiomyocytes against oxidant stress.

OBJECTIVE: Inhibitors of poly (ADP-ribose) synthetase (PARS) activity reduce the infarct size caused by regional myocardial ischaemia and reperfusion in the rabbit and rat in vivo. The mechanism of action of these inhibitors is unclear. Here we investigate the effects of the PARS inhibitor 3-aminobenzamide (3-AB) on infarct size caused by ischaemia and reperfusion of the isolated, perfused heart of the rat. We also investigate the role of PARS in the hydrogen peroxide-mediated cell injury/necrosis in rat cardiac myoblasts. METHODS: Rat isolated hearts perfused at constant pressure (80 mmHg) were subjected to 35 min of regional ischaemia and 2 h of reperfusion. Infarct size was determined at the end of the experiment using nitro-blue tetrazolium. 3-AB (300 microM) or 3-aminobenzoic acid (3-ABA, 300 microM) were infused during the reperfusion period. Rat cardiac myoblasts (H9c2 cells) were preincubated with the PARS inhibitors, 3-AB. nicotinamide (Nic) or 1,5-dihydroxyisoquinoline (ISO) or the inactive analogues 3-ABA or nicotinic acid (NicA) prior to exposure with hydrogen peroxide (1 mM). Cell injury was assessed by measuring mitochondrial respiration and cell necrosis by measuring the release of LDH. PARS activity was determined by measuring the incorporation of NAD into nuclear proteins. RESULTS: Regional ischaemia and reperfusion of the isolated rat heart resulted in an infarct size of 54% which was reduced by 3-AB, but not by 3-ABA. Exposure of rat cardiac myoblasts to hydrogen peroxide caused an increase in PARS activity and cell injury/necrosis which was attenuated by pretreatment with the PARS inhibitors. CONCLUSION: Inhibition of the activity of PARS attenuates the cell death associated with oxidant stress in rat cardiac myoblasts and heart.

Aminobenzoates↗
PubMed1999

Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents.

The cardioprotective effects of E-type prostaglandins (EPs) have been attributed to vasodilatation, inhibition of platelet and neutrophil function (EP(2) mediated), and an unknown "cytoprotective effect." We have hypothesized that selective activation of EP(3) receptors may cause cardioprotection. The prostanoid derivative ONO-AE-248 selectively binds to murine EP(3alpha) receptors expressed in Chinese hamster ovary (CHO) cells (K(i), 15 nmol/L) and prevents the rise in cAMP caused by forskolin in CHO cells (IC(50) approximately 1 nmol/L) in which the EP(3alpha) receptor had been expressed. In anesthetized rats subjected to regional myocardial ischemia for 25 or 45 minutes and 2 hours of reperfusion, infusion of ONO-AE-248 (5 microg kg(-1). min(-1) IV) caused a significant reduction in infarct size, from 60+/-3% (n=8) to 36+/-6% (n=7) and from 78+/-2% (n=11) to 58+/-4% (n=9), respectively. The reduction in infarct size caused by ONO-AE-248 in rats subjected to 25 minutes of ischemia and reperfusion was abolished by a selective inhibitor of ATP-sensitive potassium (K(ATP)) channels, 5-hydroxydecanoate (n=6), and the protein kinase C inhibitors staurosporine (n=6) and chelerythrine (n=6). In anesthetized rabbits subjected to coronary artery occlusion for 45 or 60 minutes and 2 hours of reperfusion, infusion of ONO-AE-248 (5 microg. kg(-1). min(-1) IV) caused a significant reduction in infarct size, from 61+/-2% (n=10) to 36+/-4% (n=8) and from 63+/-4% (n=7) to 42+/-4% (n=7), respectively. The reduction in infarct size caused by ONO-AE-248 in the rabbit was also abolished by 5-hydroxydecanoate. The cardioprotective effect of ONO-AE-248 in rats or rabbits was not associated with any hemodynamic effects. Selective activation of the prostanoid EP(3) receptor reduces myocardial infarct size in rodents by a mechanism(s) that may involve the activation of protein kinase C and the opening of K(ATP) channels.

Animals↗
PubMed1998

Characterization of neurons in the area of the medullary lateral reticular nucleus responsive to noxious visceral and cutaneous stimuli.

In halothane-anesthetized rats, 283 caudal medullary neurons responsive to colorectal distension (CRD) were characterized using extracellular electrodes. Neurons inhibited by CRD (n = 82) were in the area dorsal to the lateral reticular nucleus (LRN). Most neurons excited by CRD (n = 130) were located within or immediately adjacent to the LRN, were excited by noxious heat and/or noxious pinch of at least half the body surface and were called bilateral nociceptive specific (bNS) neurons. bNS neurons had accelerating responses to graded CRD (threshold: 20 +/- 2 mmHg). Ten of twelve bNS neurons tested could be antidromically activated by electrical stimulation of the midline cerebellum. Other neurons excited by CRD (n = 71) had mixed responses to cutaneous stimuli and were generally located in the area dorsal to the LRN. Increases in blood pressure due to intravenous phenylephrine did not significantly alter the spontaneous activity of neurons excited by CRD, but altered spontaneous activity (12 excited, four inhibited) in all neurons tested which were inhibited by CRD. Decreases in blood pressure produced by intravenous nitroprusside produced a reciprocal response in most neurons inhibited by CRD and had a delayed onset (20-30 s after bolus administration) excitatory effect on 21 of 27 units excited by CRD. Combined with other studies, these data suggest a role for neurons within and adjacent to the LRN in the modulation of visceral nociception. They also implicate a role for the cerebellum in visceral nociceptive processing.

Animals↗
PubMed1998

Inhibitors of the activity of poly (ADP-ribose) synthetase reduce the cell death caused by hydrogen peroxide in human cardiac myoblasts.

Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA which are caused by reactive oxygen species (ROS). Inhibitors of PARS activity reduce the degree of reperfusion injury of the heart in vivo and in vitro. Here we investigate the role of PARS in the cell death of human cardiac myoblasts caused by hydrogen peroxide. Exposure of human cardiac myoblasts to hydrogen peroxide caused a time- and concentration-dependent reduction in mitochondrial respiration (cell injury), an increase in cell death (LDH release), as well as an increase in PARS activity. The PARS inhibitors 3-aminobenzamide (3 mM), 1,5-dehydroxyisoquinoline (300 microM) or nicotinamide (3 mM) attenuated the cell injury and death as well as the increase in PARS activity caused by hydrogen peroxide (3 mM; 4 h for cell injury/death, 60 min for PARS activity) in human cardiac myoblasts. In contrast, the inactive analogues 3-aminobenzoic acid (3 mM) or nicotinic acid (3 mM) were without effect. The iron chelator deferoxamine (1-10 mM) caused a concentration-dependent reduction in the cell injury and death caused by hydrogen peroxide in these human cardiac myoblasts. Thus, the cell injury/death caused by hydrogen peroxide in human cardiac myoblasts is secondary to the formation of hydroxyl radicals and due to an increase in PARS activity. We therefore propose that activation of PARS contributes to the cell injury/cell death associated with oxidant stress in the heart.

Cell Death↗
PubMed1998

Care tracker: a new approach to nursing care in ambulatory settings.

The shift from inpatient to ambulatory settings and the increasingly large and diverse numbers of ambulatory clients require reengineering and cost-effective approaches to managing ambulatory care. With data on 921 encounters in 12 ambulatory clinics, we developed CARE TRACKER, an instrument to describe nursing encounters by type, intervention, staff, time, and cost. Distinguishing nursing from medical interventions is an appreciable improvement over the traditional practice of bundling nursing as part of overhead costs. If managers can track the care delivered, they can better calculate staffing requirements, staff mix, inservice needs, and the costs of their existing and projected services.

Ambulatory Care↗