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Biomedical subjects

G Parry

Publications and source records attributed to G Parry.

At least 37 records · Page 2Linked to original sources

Novel auxin transport inhibitors phenocopy the auxin influx carrier mutation aux1.

The hormone auxin is transported in plants through the combined actions of diffusion and specific auxin influx and efflux carriers. In contrast to auxin efflux, for which there are well documented inhibitors, understanding the developmental roles of carrier-mediated auxin influx has been hampered by the absence of specific competitive inhibitors. However, several molecules that inhibit auxin influx in cultured cells have been described recently. The physiological effects of two of these novel influx carrier inhibitors, 1-naphthoxyacetic acid (1-NOA) and 3-chloro-4-hydroxyphenylacetic acid (CHPAA), have been investigated in intact seedlings and tissue segments using classical and new auxin transport bioassays. Both molecules do disrupt root gravitropism, which is a developmental process requiring rapid auxin redistribution. Furthermore, the auxin-insensitive and agravitropic root-growth characteristics of aux1 plants were phenocopied by 1-NOA and CHPAA. Similarly, the agravitropic phenotype of inhibitor-treated seedlings was rescued by the auxin 1-naphthaleneacetic acid, but not by 2,4-dichlorophenoxyacetic acid, again resembling the relative abilities of these two auxins to rescue the phenotype of aux1. Further investigations have shown that none of these compounds block polar auxin transport, and that CHPAA exhibits some auxin-like activity at high concentrations. Whilst results indicate that 1-NOA and CHPAA represent useful tools for physiological studies addressing the role of auxin influx in planta, 1-NOA is likely to prove the more useful of the two compounds.

Arabidopsis↗

Health status of Gypsy Travellers.

BACKGROUND: Although previous studies suggest that Gypsy Travellers have poorer health status and excess mortality compared with the general population, there is no epidemiological evidence using validated measures in this nomadic ethnic group. The aim of this study was to compare the health status of traditional Gypsy Travellers with norms from the UK population, and with a concurrent comparison group using the Euroqol health status measure (EQ-5D). METHODS: Eighty-seven adult Gypsy Travellers were matched for age and sex with English or Irish residents, registered with an urban general practice in an area of high social deprivation. Both samples completed the EQ-5D questionnaire by interview. A comparison was also made with normative data from the UK general population. RESULTS: Travellers had poorer health status than their settled counterparts on two of the five dimensions (mobility and activity) but not on the overall summary score. Travellers reported significantly poorer health than the matched comparison group on the EQ-5D visual analogue scale. Both the Travellers and the comparison group had much poorer health status on the EQ-5D index than the UK population norms, even when compared with the lowest socioeconomic group. CONCLUSIONS: Health status of Gypsy Travellers was significantly poorer than in the lowest socio-economic UK population group, but was not so markedly different from a concurrent, matched, socially deprived resident group. Gypsy Travellers did have poorer health status than matched comparators in relation to mobility, activity and perception of overall health. Quantitative assessment of health status in the Traveller community is feasible.

Activities of Daily Living↗

Evidence on the efficacy of insert earphone and sound field VRA with young infants.

Visual reinforcement audiometry (VRA) with insert-earphone stimulus delivery provides a means of obtaining early ear-specific information on the auditory status of infants. The aim of this study was to investigate the efficacy of VRA in young infants, and to compare the use of sound field and insert-earphone stimulus presentation. VRA was performed on 41 normally developing infants aged between 20 and 42 weeks. Infants were tested in the sound field (n=22) and with insert earphones (n=19). Results showed significantly more minimum response levels (MRLs) obtained with sound field testing, and with older children. Nevertheless, in the insert-earphone group, 36% of those aged 32 weeks or more gave two or more MRLs, and 25% of the infants aged 25 weeks or less gave one or more MRLs. This study provides data from developmentally normal infants which confirms the efficacy of insert-earphones as well as sound field VRA with 32-42-week-olds, with reasonable expectation of success. The data in this study also suggest that VRA could be usefully employed for younger infants aged approximately 20-26 weeks where information, although less easily obtained, may be of particular value to early diagnosis and habilitation.

Audiometry↗

Toward the development of a clinically useful approach to psychotherapy research.

The controversial move toward the development of a consensus on evidence-based or empirically supported therapies may be seen as an international crisis facing psychotherapists. Researchers long have complained that practicing therapists all too often continue to guide what they do therapeutically on the basis of their clinical experience and not the available research findings. Practicing therapists long have complained that therapy research bears only a remote resemblance to what goes on in actual clinical practice and that research reports are written for other researchers, not for clinicians. In the hope of turning our current crisis into an opportunity, this panel involved a dialogue that was designed to bridge this clinical-research gap.

Decision Making↗

UK neonatal intensive care services in 1996. On behalf of the UK Neonatal Staffing Study Collaborative Group.

A census of activity and staff levels in 1996 was conducted in UK neonatal units and achieved a 100% response from 246 units. Among the 186 neonatal intensive care units, the median (interquartile range) number of total cots was 18(14-22); level 1 intensive care cots 4(2-6); total admissions 318(262-405); very low birthweight admissions 40(28-68); and the number ventilated or given CPAP by endotracheal tube 52(32-83). Forty six (25%) intensive care units lacked the recommended minimum of one consultant with prime responsibility for neonatal medicine. As a conservative estimate 79% of intensive care units had a lower nursing provision than that recommended in previously published guidelines. There was substantial variation in activity and staffing levels among units.

Hospital Bed Capacity↗

AtPIN2 defines a locus of Arabidopsis for root gravitropism control.

The molecular mechanisms underlying gravity perception and signal transduction which control asymmetric plant growth responses are as yet unknown, but are likely to depend on the directional flux of the plant hormone auxin. We have isolated an Arabidopsis mutant of the AtPIN2 gene using transposon mutagenesis. Roots of the Atpin2::En701 null-mutant were agravitropic and showed altered auxin sensitivity, a phenotype characteristic of the agravitropic wav6-52 mutant. The AtPIN2 gene was mapped to chromosome 5 (115.3 cM) corresponding to the WAV6 locus and subsequent genetic analysis indicated that wav6-52 and Atpin2::En701 were allelic. The AtPIN2 gene consists of nine exons defining an open reading frame of 1944 bp which encodes a 69 kDa protein with 10 putative transmembrane domains interrupted by a central hydrophilic loop. The topology of AtPIN2p was found to be similar to members of the major facilitator superfamily of transport proteins. We have shown that the AtPIN2 gene was expressed in root tips. The AtPIN2 protein was localized in membranes of root cortical and epidermal cells in the meristematic and elongation zones revealing a polar localization. These results suggest that AtPIN2 plays an important role in control of gravitropism regulating the redistribution of auxin from the stele towards the elongation zone of roots.

Amino Acid Sequence↗

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma.

We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

Cancer Vaccines↗

Orthotopic cardiac transplantation for the failing Fontan circulation.

OBJECTIVE: Modified Fontan procedures are now employed in several conditions unsuitable for bi-ventricular repair. Selection criteria have been relaxed. The procedure is palliative. Longterm outlook is unknown. This study evaluated factors associated with the development of a failing Fontan circulation and transplantation results. METHODS: Retrospective review of patients referred to a single centre for cardiac transplant assessment. RESULTS: Between 1985 and 1996, 46 of 448 cardiac transplants were performed for congenital heart disease. Nine of these were performed in patients with a failing Fontan circulation (four adults, five children). In six cases, the dominant ventricle had left ventricular (LV) morphology. Congenital anomalies included double outlet right ventricle (three cases), double inlet left ventricle (two cases), tricuspid atresia (two cases), and pulmonary atresia with intact ventricular septum (one case). Fontan procedures were performed in absence of sinus rhythm (four cases), atrio-ventricular (AV) valve regurgitation (two cases), aortic regurgitation and systolic LV dysfunction (one case), elevated mean pulmonary artery pressure (one case), and older age (>7 years, eight cases). Three patients required early re-operation and two needed permanent pacing. Subsequent deterioration associated with loss of sinus rhythm (four cases) and progressive AV valve regurgitation (seven cases) led to transplant assessment (at < 1 year, five cases; at 2-12 years, four cases). All patients were listed for transplantation. Three patients required intravenous inotropic support and three patients with lymphocytotoxic antibodies needed prospective crossmatching. Donor cardiectomy was modified to facilitate implantation. The recipient operation involved pulmonary artery reconstruction (using pericardium), modified atrial and direct caval anastomoses. Three patients died within 24 h of surgery (two graft failures, one haemorrhage). In operative survivors (n = 6), intensive care stay was 3-16 days, and hospital stay ranged from 14 to 32 days. There have been no subsequent deaths (follow up, 0.5-4.7 years). CONCLUSION: In high-risk Fontan candidates, transplantation may be preferable at the outset. Previous surgery, lymphocytotoxic antibodies, indeterminate pulmonary vascular resistance, emergency status, sub-optimal donor selection, and perioperative bleeding contribute to peri-operative mortality. In survivors, the outcome remains very encouraging.

Antilymphocyte Serum↗

Declining need for pacemaker implantation after cardiac transplantation.

The need for permanent pacemaker implantation was retrospectively reviewed in 436 consecutive cardiac transplant recipients at our center between 1985 and 1998. The incidence of pacemaker implantation was examined in three arbitrarily defined periods: period 1, 1985-1990, before a review of pacemaker implantation policy; period 2, 1991-1995, after a change in policy to delay pacemaker implantation resulting from the review; and period 3, 1996-1998, after audit of this policy change, and the introduction of a change in surgical technique, from the standard atrial anastomosis to the bicaval anastomosis. Pacemaker implantation was not required in any recipient after the change in surgical technique, suggesting that the bicaval technique preserves sinus node function much better than does the standard atrial anastomosis.

Cardiac Pacing, Artificial↗

Role of orthotopic heart transplantation in the management of patients with recurrent ventricular tachyarrhythmias following myocardial infarction.

OBJECTIVE: To report the outcome of an intention to treat by heart transplantation strategy in two groups of patients after infarction, one with both left ventricular failure (LVF) and ventricular tachyarrhythmias (VTA) (group A) and the other with progressive LVF following antiarrhythmic surgery for VTA (group B). PATIENTS AND METHODS: Group A comprised 17 consecutive patients for whom transplantation was considered the best primary non-pharmacological treatment; group B comprised five consecutive patients assessed and planned for transplantation after antiarrhythmic surgery. RESULTS: In group A, eight patients underwent transplantation and all survived the first 30 day period. At median follow up of 55 months (range 11 to 109) seven of this subgroup were still alive. Five patients died of recurrent VTA before transplantation, despite circulatory support. In the face of uncontrollable VTA, four of these underwent "high risk" antiarrhythmic surgery while awaiting transplantation: three died of LVF within 30 days and one was saved by heart transplantation two days after arrhythmia surgery. Mortality for the transplantation strategy in group A patients was 47% by intention to treat analysis. Quality of life in the eight actually transplanted, however, was good and only one died during median follow up of 56 months. The five patients in group B were accepted for transplantation for progressive LVF at a median of 21 months (range 12 to 28) after antiarrhythmic surgery. One died of LVF before transplantation, 22 months after initial surgery; another died of high output LVF three days after transplantation. Thus mortality of the intended strategy was 40%. The three transplanted patients are alive and well at 8-86 months. CONCLUSIONS: Although the short and medium term outcome in category A or B patients who undergo transplantation is good, the overall success of the transplantation strategy in category A patients is limited by lack of donors in the short time frame in which they are required.

Adult↗

Toward earlier diagnosis of amyotrophic lateral sclerosis: revised criteria. rhCNTF ALS Study Group.

We modified the World Federation of Neurology (WFN) diagnostic criteria for ALS to facilitate early diagnosis and used these criteria for enrollment of ALS patients in a clinical trial. The criteria developed required lower motor neuron (LMN) involvement in at least two limbs and upper motor neuron involvement in at least one region (bulbar, cervical, or lumbosacral). The EMG finding of fibrillation potentials was required for evidence of LMN involvement. Electrodiagnostic studies, neuroimaging, and laboratory studies were also used to exclude disorders that might mimic ALS. Using these criteria, the diagnosis of ALS was made at a mean time of 9.7 months from onset of symptoms, which compares favorably with the 12-month period cited in the literature. Using clinical assessment at completion of the trial, the diagnosis of ALS was believed to be accurate in those patients entered in the trial. However, pathologic confirmation of the diagnosis of ALS was not obtained. Based on our preliminary experience, we propose that these ALS diagnostic criteria will facilitate early diagnosis of ALS. Future studies should prospectively compare these criteria with the WFN criteria currently in use.

Amyotrophic Lateral Sclerosis↗