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Biomedical subjects

J Taylor

Publications and source records attributed to J Taylor.

At least 19 recordsLinked to original sources

Risk of herpes simplex virus type 2 acquisition increases over early adulthood: evidence from a cohort study.

UNLABELLED: DESIGN/ SETTING: A cohort study of 1037 people born in Dunedin, New Zealand, in 1972 or 1973. PARTICIPANTS: At assessment at age 32 years, 884 participants (432 women and 452 men; 87.1% of the surviving cohort) provided both sera and information on sexual behaviour. MAIN OUTCOME MEASURES: The proportion of participants with antibodies to HSV-2 infection at ages 26 and 32 years was measured, and the incidence rates from first coitus to age 26 years and from age 26 to 32 years calculated, adjusting for the number of sexual partners and same-sex contact in these age periods. RESULTS: At age 32 years, 14.6% of men and 22.5% of women had antibodies to HSV-2. The incidence rates for men and women from first coitus to age 26 years were, respectively, 6.5 and 14.3 per 1000 person-years. The incidence rates for men and women from age 26-32 years, respectively, were 14.3 and 15.8 per 1000 person-years. When adjusted for sexual behaviour, the incidence rate ratio, comparing the older with the younger age periods, was 2.9 (95% confidence interval (CI) 1.7 to 4.9) for men and 2.0 (1.2 to 3.4) for women. The adjusted incidence rate ratio when comparing women to men from first coitus to age 26 years was 2.5 (1.6 to 4.0), and from age 26-32 years was 1.3 (0.78 to 2.2). A test for interaction indicated that men and women had different patterns of incidence over time (p = 0.039). CONCLUSION: In the general population, the risk of acquiring HSV-2 infection seems to increase with age at least to the early 30s, and differences in risk of acquisition for women compared with men become less with age. Health promotion and treatment to control HSV-2 infection should be aimed at all ages, not just at the young.

Adult↗

Modifications to improve the efficiency of zona-free mouse nuclear transfer.

In the present study, some modifications were made to the zona-free nuclear transfer technique in the mouse in order to achieve greater efficiency. Firstly, a 1-h interval was allowed between cumulus removal and zona pellucida digestion. Secondly, acid Tyrode's was selected for zona pellucida removal, because contrary to pronase, it allows embryo survival during parthenogenic activation in the absence of calcium. Even when the exposure time to pronase was reduced to as little as 1 min or washed with fetal calf serum to inhibit the enzyme, the percentage of lysis during activation in the absence of calcium was still very high. Thirdly, electrofusion was performed at room temperature (21 degrees C), instead of 30 degrees C as in our previous experiments. Finally, embryos were cultured in groups of 12-15, instead of individually, using a "well of the wells" system during activation and culture. When compared, parthenogenic activated control embryos showed an increase in the development to blastocyst when cultured in pairs instead of individually. By the end of the experiments and using embryonic stem (ES) cells, there was a significant increase in fusion rate (1.5-fold increase) and in development to morula/blastocyst from cleaved reconstructed embryos (1.5-fold increase) when compared with the results before the modifications. A 2.4-fold increase in overall efficiency was achieved from the oocyte to morula/blastocyst stages.

Animals↗

Peritoneal macrophages suppress T-cell activation by amino acid catabolism.

T-lymphocyte activation triggered by anti-CD3, endogenous or exogenous superantigen, and mitogens was suppressed in a cell-dose-dependent fashion by peritoneal cavity (PerC) leucocytes. Study of lymphocyte-deficient mice and the use of multiparameter fluorescence-activated cell sorter analyses revealed that macrophages were responsible for this form of immune regulation. Interferon-gamma was essential to trigger suppression, which, by enzyme inhibition studies, was shown to be the result of tryptophan and arginine catabolism. These results illustrate that macrophages, which are classically defined by their innate effector function as antigen-presenting cells, have the potential to temper adaptive immunity.

Animals↗

A cluster of parvovirus B19 infections in renal transplant recipients: a prospective case series and review of the literature.

Up to 9% of renal transplant recipients have severe multifactorial erythropoietin-resistant anemia. Human parvovirus B19 (PVB19) infection can cause severe anemia and is likely underreported. Sparse information on epidemiology and management in this population exists. To address these issues, after our first index case, we modified our clinical practice to prospectively screen patients with persistent hemoglobin (Hb) <10 mg/dL for PVB19 infection after excluding common causes of anemia including erythropoietin resistance. Potentially infected patients were further evaluated by serology, qualitative polymerase chain reaction (quPCR) and bone marrow biopsy (BMB) for cytomegalovirus, Epstein-Barr virus, PVB19 and other etiologies. Over 3 months, 212 kidney recipients visited outpatient clinics. Of 52 recipients with anemia, 8 had an Hb <10 mg/dL with erythropoietin resistance and were screened for PVB19 infection. Three cases had PVB19 infection by quPCR and often-inconclusive serology/BMB results. Cases had immunosuppression reduced and received IVIG (0.5 gm/kg x 4 doses) with recovery from anemia, viral clearance in two cases and one recurrence. PVB19-mediated anemia occurred in up to three out of eight (38%) screened kidney recipients with Hb <10 mg/dL resistant to erythrypoietin. We recommend prospective risk stratification for this population, high indices of suspicion using at least qualitative techniques for diagnosis and treatment goal for viral eradication.

Adult↗

Prevalence of infection with herpes simplex virus types 1 and 2 in Australia: a nationwide population based survey.

BACKGROUND: Studies demonstrating previous herpes simplex virus (HSV) type 2 infection as a risk factor for HIV transmission, and the development of a HSV vaccine candidate, have emphasised the need for worldwide population based studies of HSV seroprevalence. The only nationwide seroprevalence studies have been conducted in the United States. METHODS: An Australia-wide, population based study of HSV-1 and HSV-2 seroprevalence was conducted, using serum and sociodemographic data collected between 1999-2000, for a representative study of risk factors for diabetes in over 11 000 adults. A stratified random sample of 4000 was tested for HSV-2 and 1000 for HSV-1, with sampling and weighting for various demographic factors. RESULTS: Seroprevalence of HSV-2 in Australian adults was 12%. Prevalence in women (16%) was twice that in men (8%). Rural populations had a lower prevalence (9%) than metropolitan (13%), and Indigenous had a higher prevalence (18%) than the non-Indigenous populations (12%). The seroprevalence of HSV-1 was 76% with significant differences by age group, sex and Indigenous status. CONCLUSION: These are the first nationwide data to compare with US studies. HSV-2 infection is less common in Australia than the United States, and this will allow planning for combating HIV transmission in high prevalence populations in northern Australia. In addition, the high HSV-1 seroprevalence will be important for future deployment of genital herpes vaccines.

Adult↗

Flexible trainees in Scotland.

INTRODUCTION: Demand for flexible training is increasing. The contribution of such trainees to the trained medical workforce is not clear. METHODS: All full time and flexible trainees in Scotland were 'tracked' at the completion of training. RESULTS: 80% of flexible trainees took up a consultant post of which 93% were in Scotland. 82% of full time trainees took up a consultant post of which 80% were in Scotland. DISCUSSION: Flexible trainees become consultants at the same rate as their full time counterparts. They are commonly geographically tied and are therefore more likely to remain in Scotland and contribute to retention of doctors in this country.

Attitude of Health Personnel↗

The effect of selective sst1, sst2, sst5 somatostatin receptors agonists, a somatostatin/dopamine (SST/DA) chimera and bromocriptine on the "clinically non-functioning" pituitary adenomas in vitro.

The aim of the work was to investigate the effects of somatostatin analogs acting selectively on sst1 (BIM-23926), sst2 (BIM-23120) and sst5 (BIM-23206) receptor subtypes on the viability of "clinically non-functioning" pituitary adenomas in vitro. The effects of native SST (SST-14), a SST/DA chimera (BIM-23A387) and a D(2)-dopamine receptor agonist bromocriptine (BC) were also examined. The study was performed on 10 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". A part of each tumor was mechanically dispersed and digested with collagenase to isolate the tumoral cells. Another part of each tumor was fixed, embedded in paraffin and immunostained to reveal the pituitary hormones and SST receptor subtypes (sst1, sst2A, sst2B, sst3, sst4, sst5). The tumoral cell suspensions were incubated for 24 h with the substances mentioned above. The quantity of viable cells was estimated using the EZ4U system. The results were compared with the immunohistochemical evaluation of the hormonal profile of adenoma and the sst receptor subtype immunoreactivities present. The findings indicate that selective sst1, sst2 and sst5 receptors agonists, SST/DA chimera and D(2)-dopamine receptor agonist bromocriptine affect the viability of some, but not all, "clinically non-functioning" pituitary adenomas in vitro. The most effective was bromocriptine. The investigated somatostatin analogs including SST/DA chimera exerted roughly similar inhibitory effects. Further studies are needed to fully evaluate the potential usefulness of these compounds in the pharmacological treatment of "non-functioning" pituitary tumors.

Adenoma↗

Identifying vibrations that destabilize crystals and characterize the glassy state.

High-resolution inelastic neutron scattering was used to identify major sources of low-frequency vibrations in zeolite crystals. Dispersed and nondispersed modes were found, both of which are prominent in the early stages of compressive amorphization but decline dramatically in strength once a glass of conventional density is created. By identifying the dispersed modes with the characteristic vibrations of the various secondary building units of zeolitic structures, the Boson peak, a characteristic of the glassy state, can be attributed to vibrations within connected rings of many different sizes. The nondispersed phonon features in zeolites, retained in the amorphized glass, were also replicated in silica. These modes are librational in origin and are responsible for destabilizing the microporous crystalline structure, for converting the resulting glass from a low- to a high-density phase, and for the associated changes in network topology that affect the Boson peak.

Journal Article↗

Endogenous ghrelin regulates episodic growth hormone (GH) secretion by amplifying GH Pulse amplitude: evidence from antagonism of the GH secretagogue-R1a receptor.

Ghrelin was purified from rat stomach as an endogenous ligand for the GH secretagogue (GHS) receptor. As a GHS, ghrelin stimulates GH release, but it also has additional activities, including stimulation of appetite and weight gain. Plasma GH and ghrelin secretory patterns appear unrelated, whereas many studies have correlated ghrelin variations with food intake episodes. To evaluate the role of endogenous ghrelin, GH secretion and food intake were monitored in male rats infused sc (6 mug/h during 10 h) or intracerebroventricularly (5 microg/h during 48 h) with BIM-28163, a full competitive antagonist of the GHS-R1a receptor. Subcutaneous BIM-28163 infusion significantly decreased GH area under the curve during a 6-h sampling period by 54% and peak amplitude by 46%. Twelve hours after the end of treatment these parameters returned to normal. Central treatment was similarly effective (-37 and -42% for area under the curve and -44 and -49% for peak amplitude on the first and second days of infusion, respectively). Neither peripheral nor central BIM-28163 injection modified GH peak number, GH nadir, or IGF-I levels. In this protocol, food intake is not strongly modified and water intake is unchanged. Subcutaneous infusion of BIM-28163 did not change plasma leptin and insulin levels evaluated at 1200 and 1600 h. On the contrary, central BIM-28163 infusion slightly increased leptin and significantly increased insulin concentrations. Thus, endogenous ghrelin, through GHS-R1a, acts as a strong endogenous amplifier of spontaneous GH peak amplitude. The mechanisms by which ghrelin modifies food intake remain to be defined and may involve a novel GHS receptor.

Animals↗

Tetrahedral order in homologous disaccharide-water mixtures.

The present work aims at evidencing the "kosmotrope" nature of trehalose through the analysis of inelastic neutron scattering measurements on trehalose and sucrose water solutions at different temperatures. Neutron spectra were collected by using the spectrometer MARI at the ISIS pulsed neutron source of the Rutherford Appleton Laboratory (Chilton, UK). To study the structural modifications induced on the tetrahedral hydrogen-bond network of water by homologous disaccharides, as a first step, the vibrational properties of pure water at different temperatures have been investigated. In particular, the temperature behavior of the intramolecular OH stretching mode has been analyzed. Successively, the vibrational properties for pure water have been compared with those of the sugar water solutions focusing the attention on the tetrahedral network-forming tendency. Finally, the obtained findings have been compared with previous Raman scattering evidences, and the results interpreted in the frame of recent molecular dynamics simulation works.

Journal Article↗

The foot-and-mouth disease epidemic in Dumfries and Galloway, 2001. 2: Serosurveillance, and efficiency and effectiveness of control procedures after the national ban on animal movements.

After the foot-and-mouth disease (FMD) epidemic in Dumfries and Galloway in south-west Scotland in 2001, serosurveillance of sheep remaining in the 3 km radius Protection Zones around Infected Premises (IPS), and within a 10 km radius of IPS, revealed no evidence of infection. The epidemic was brought under control by a range of traditional techniques: slaughter of all animals on IPS and of veterinary-assessed Dangerous Contacts (DCS), movement restrictions, biosecurity, tracing of potential sources and spread of virus, and surveillance of At-Risk premises. Novel pre-emptive slaughter of FMD-susceptible animals on premises contiguous to IPS, and small ruminants and pigs on premises within 3 km of IPSs, commenced after the epidemic had peaked. Most of the traditional control procedures were undertaken quickly and with appropriate priority. Animals on IPS were usually slaughtered within one day of confirmation, and veterinary-assessed DCS within two days of confirmation of relevant IPS (a median of two days). The pre-emptive contiguous and 3 km culls took somewhat longer (medians of five and 17 days, respectively). IPS were most commonly identified as a result of reporting by farmers or their veterinarians (72 per cent of IPS); veterinary clinical patrols identified 16 per cent, while veterinary assessment of DCS and tracing each identified 5 per cent. No evidence of infection was found on any pre-emptively contiguously culled premises, and IPS were declared only on three 3 km cull premises. The time from estimated first lesion to end of slaughter on an IP was found, by regression analysis, to be a key component in effective control, manifested by a reduction in the estimated dissemination rate (EDR); there was little evidence that the intensity of contiguous culling affected the EDR. Patrols and serological surveillance of residual animals within 10 km of IPS, supported by more extensive evidence from elsewhere in the UK, suggested that cryptic infection in sheep was not widespread. Ultimately, there was insufficient evidence to support the effectiveness of 3 km pre-emptive culling as a control procedure.

Abattoirs↗

The foot-and-mouth disease epidemic in Dumfries and Galloway, 2001. 1: Characteristics and control.

The foot-and-mouth disease epidemic in Dumfries and Galloway in south-west Scotland comprised 177 infected premises (IPS) in 24 geographical clusters, and ran from March 1 until May 23, 2001. Initial seeding of infection was by livestock (predominantly sheep) that had passed through Longtown Market in adjacent Cumbria. Thereafter, spread within existing, and to new, clusters was associated with the movement of personnel and vehicles, with further transmission by Longtown Market contacts and across common boundaries. Sheep and cattle premises were equally affected. After the peak of the epidemic at the beginning of the third week of March, the upper possible limit of attack rates for premises contiguous to IPS, and premises within 3 km, remained around 10 per cent, with new clusters emerging more distantly. Control procedures included traditional methods of slaughter of all animals on IPS and, elsewhere, of animals considered by veterinary assessment to be Dangerous Contacts; movement restrictions; enhanced biosecurity; tracing of potential sources and spread of virus; and surveillance of premises subsequently considered at risk. These methods were supplemented by the novel pre-emptive slaughter, without veterinary assessment, of all susceptible livestock on all premises contiguous to IPS, and of small ruminants and pigs within a 3 km radius (known as the Protection Zone) around IPS. In total, approximately 80,000 cattle, 564,000 sheep, 2600 pigs and 500 goats were slaughtered, the novel methods accounting for 29 per cent of all cattle and 75 per cent of all sheep killed. Limitations of existing national databases necessitated the development of local databases to administer control procedures.

Animals↗

Development of a zona-free method of nuclear transfer in the mouse.

In the present study, a zona-free nuclear transfer (NT) technique, which had been originally developed in cattle, was modified for the mouse. Steps involved in this approach include removing the zona pellucida and enucleating without a holding pipette; sticking donor cells to the cytoplast before electric pulses are applied to fuse them and culturing reconstructed embryos individually in single droplets, to prevent aggregation. Control zona-free and zona-intact embryos from mated donors showed no significant difference in development to blastocyst, but did show reduced development to term. Removal of the zona pellucida affected the response to activation by strontium in the absence of calcium as a significant proportion of zona-free control oocytes and embryos reconstructed by NT lysed during this treatment. A comparison between cumulus and ES cells as donor cells revealed significant differences in fusion efficiency (58.1 +/- 4.0%, n = 573 vs. 42.9 +/- 2.2%, n = 2064, respectively, p < 0.001), cleavage (77.2 +/- 3.4%, n = 334 vs. 40.8 +/- 2.7%, n = 903, respectively, p < 0.001) but not for development to morula/blastocyst (8.7 +/- 2.1%, n = 334 vs. 13.9 +/- 1.8%, n = 903, respectively, p < 0.1). The stage at which embryo development arrested was also affected by donor cell type. A majority of embryos reconstructed from cumulus cells arrested at two-cell stage, usually with two nuclei, whereas those reconstructed from ES cells arrested at one-cell stage, usually with two pseudo-pronuclei. After transfer of ES cell-derived NT embryos, a viable cloned mouse was produced (3.0% of transferred embryos developed to term). These observations establish that a zona-free cloning approach is possible in the mouse, although further research is required to increase the efficiency.

Animals↗

Pall eBDS: an enhanced bacterial detection system for screening platelet concentrates.

Bacterial contamination of blood components remains a significant problem in transfusion medicine. The Pall enhanced bacterial detection system (Pall eBDS) detects the presence of bacteria in leucodepleted platelet concentrates by measuring the reduction of oxygen in the sample, due to aerobic bacterial growth. Pooled platelet concentrates were spiked at 10 cfu mL(-1) with 10 organisms (one species per bag). Pall eBDS pouches were inoculated with the spiked platelet concentrates. After 24 and 30 h of incubation, the oxygen level was measured. A further set of pouches were taken from the inoculated platelet concentrates at 24 h. Incubation and reading intervals were as for the initial set of pouches. A sensitivity study was also performed comparing the Pall eBDS with the BacT/ALERT system. Spiking at 10 cfu mL(-1) and immediately sampling into Pall eBDS pouches resulted in 97.6 and 100% detection after an incubation period of 24 and 30 h, respectively. After 24 h of incubation of the spiked platelet concentrates and then sampling into Pall eBDS pouches, 99.1% detection was obtained after incubation for both 24 and 30 h. The sensitivity of the Pall eBDS and BacT/ALERT is similar and in the order of 1 cfu mL(-1). Implementation of either BacT/ALERT or Pall eBDS for routine screening of platelet concentrates has the potential to further increase the safety of the blood supply.

Bacteria, Aerobic↗

Outpatient treatment with subcutaneous interleukin-2, interferon alpha and fluorouracil in patients with metastatic renal cancer: an Australian experience.

BACKGROUND: Metastatic renal cell cancer has a poor prognosis and survival. Conventional cytotoxic chemotherapy has no impact on survival and response rates are low. Biologic agents are the most active in treating this disease. We report the feasibility of administering a combination of interferon alpha, subcutaneous interleukin-2 and 5Fluorouracil in the outpatient setting to patients with metastatic renal cell cancer. RESULTS: Between September 1996 and August 2003, fourteen patients were treated with this combination: ten males and four females with a median age of 50 (42-66). Thirteen patients had Eastern Cooperative Oncology Group performance scores of 0 or 1. Ten patients had had nephrectomies. Six patients had undergone prior treatments with chemotherapy or hormonal therapy. Twenty-two cycles were administered (median 1, range of 1-4). Three patients achieved partial response, eight patients had stable disease, and three had progressive disease. The duration of response in patients with stable disease was (3, 3+, 4, 4+, 5+, 6, 10, 11 months) and for the patients with a partial response was 2+, 11 and 12 months. Toxicities with this combination were predictable. There were no treatment-related deaths and no episodes of febrile neutropenia. One patient ceased treatment as a result of toxicity. Fatigue was the most common side-effect. Myalgias, fever and rigors occurred within 6-12 h of administration of interleukin-2, and resolved within 12 h. Grade 1-2 nausea and vomiting occurred in most patients. Four patients had transient asymptomatic transaminitis, which resolved spontaneously. As a result of toxicity, one patient had treatment ceased in his 6th week. CONCLUSION: This combination was feasible, well tolerated and manageable in an outpatient setting.

Administration, Cutaneous↗

PYY3-36 as an anti-obesity drug target.

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Animals↗

Follow-up of polytetrafluoroethylene arteriovenous fistulae for haemodialysis.

The polytetrafluoroethylene (PTFE) arteriovenous fistula allows vascular access for haemodialysis where a primary fistula or brachio-basilic vein transposition is not possible. We report patency rates and complications associated with these prosthetic grafts. Fifty-nine upper limb PTFE grafts in 48 patients were evaluated with a mean follow-up of 19 months (range 2-54 months). Three grafts (5%) were never used. The primary patency rate at 6 weeks was 90%. Cumulative secondary patency rates were 66% at 6 months, 36% at 12 months, 17% at 18 months, 3% at 24 months and 2% at 30 months. None of the grafts had remained patent at 3 years. Forty-six percent of the grafts studied thrombosed at least once and 32% became infected. Although the initial primary patency rate achieved compares favourably with that reported for brachio-basilic transposition fistulae, this study confirms that the use of prosthetic material is associated with a poor overall patency rate and high risk of complications. All options using autologous vein should be exhausted before considering prosthetic material.

Adolescent↗