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Biomedical subjects

S Parkinson

Publications and source records attributed to S Parkinson.

16 recordsLinked to original sources

Oblique pelvic osteotomy in the exstrophy/epispadias complex.

We reviewed retrospectively 45 patients (46 procedures) with bladder exstrophy treated by bilateral oblique pelvic osteotomy in conjunction with genitourinary repair. The operative technique and post-operative management with or without external fixation are described. A total of 21 patients attended a special follow-up clinic and 24 were interviewed by telephone. The mean follow-up time was 57 months (24 to 108). Of the 45 patients, 42 reported no pain or functional disability, although six had a waddling gait and two had marked external rotation of the hip. Complications included three cases of infection and loosening of the external fixator requiring early removal with no deleterious effect. Mid-line closure failed in one neonate managed in plaster. This patient underwent a successful revision procedure several months later using repeat osteotomies and external fixation. The percentage pubic approximation was measured on anteroposterior radiographs pre-operatively, post-operatively and at final follow-up. The mean approximation was 37% (12% to 76%). It varied markedly with age and was better when external fixation was used. The wide range reflects the inability of the anterior segment to develop naturally in spite of close approximation at operation. We conclude that bilateral oblique pelvic osteotomy with or without external fixation is useful in the management of difficult primary closure in bladder exstrophy, failed primary closure and secondary reconstruction.

Age Factors↗

Radon in the workplace: implications of studies of post-remediation monitoring.

Radon gas has been shown to cause an increased incidence of lung cancer. In affected areas, levels in the overground workplace can be sufficiently high to be a health risk and remediation is required. In the UK, the workplace Action Level is 400 Bq m(-3). The variation of radon levels in the workplace was studied both before and after remediation. In most rooms, remediation resulted in a greater reduction at night than during the working day. The dose reduction, and therefore the health benefit, to workers is less than that predicted by the drop in radon averaged over 24 h. In order to obtain a health benefit to 75% of workers in our series, the 24 h average radon level in each room must be reduced to <225 Bq m(-3). It is recommended that UK Regulatory Agencies adopt a post-remediation workplace Action Level of 225 Bq m(-3).

Air Pollutants, Occupational↗

Inhibitors of caspase homologues suppress an apoptotic phenotype in cultured rabbit corpora lutea.

Apoptosis is a morphologically defined type of cell death initiated by various stimuli that results in the activation of caspases (cysteine-containing aspartate-specific proteases). In the present study, it was determined that caspases are present during, and play a role in, corpus luteum (CL) apoptosis in vitro. Pseudopregnancy was induced in rabbits with 100 IU human chorionic gonadotrophin. On Day 11 of pseudopregnancy, CL were isolated and cultured for 0, 2, 4, 6, and 8 h in the absence of trophic support to induce spontaneous apoptosis. Total RNA was extracted and analysed for caspase-I expression by Northern blot analysis. The results demonstrated caspase-I expression from 4 h. In the second part of the study, CL were incubated without trophic support for 4 h with increasing concentrations of three general caspase inhibitors, sodium aurothiomalate (SAM), iodoacetic acid (IAA) and N-tosyl-L-phenylalanylchloromethylketone (TPCK), and two specific caspase inhibitors, N-acetyl (Ac)-Tyr-Val-Ala-Asp (YVAD)-chloromethylketone (CMK) (Ac-YVAD-CMK) and Ac-Asp-Glu-Val-Asp (DEVD)-aldehyde (CHO) (Ac-DEVD-CHO). At completion, DNA was isolated and integrity assessed. Treatment of CL with SAM, IAA or Ac-DEVD-CHO effectively suppressed apoptotic DNA fragmentation. The final component of the study was to examine caspase-3 protein expression. Western blot analysis revealed a significant increase in caspase-3 expression over the experimental time-course. The results of the present study clearly demonstrate a time-dependent link between the caspases, specifically caspase-3 and spontaneous apoptosis in the rabbit CL.

Amino Acid Chloromethyl Ketones↗

Do the UK workplace Radon Action Levels reflect the radiation dose received by the occupants?

In the UK, Action Levels for radon have been established at 400 Bq m(-3) for the workplace and 200 Bq m(-3) for the home. We have estimated the dose received by occupants of rooms with radon levels near or above the Action Level, using hourly radon readings, and a questionnaire to record occupancy. In the workplace, results for 73 staff suggest that doses are lower than expected, partly due to part-time working and partly due to the mobility of staff. The 75% quantile for the series, corrected to a 37 hour week, is 5.2 mSv at 400 Bq m(-3). Compared to the current annual limit for radiation workers, the Action Level could be increased, but the current Action Level is compatible with the recent EEC Directive requiring a lower dose limit. However, when raised radon levels in the workplace were reduced by remediation in the series we studied, the dose reduction to staff was consistently around half of the radon level reduction. Although it would be appropriate to study more locations, this suggests an Action Level for remediated workplaces of 200 Bq m(-3). Finally, in a limited series of dose assessments in domestic properties, we found that doses could considerably exceed 5 mSv at the 200 Bq m(-3) Action Level, primarily because the sample included an example of high occupancy, in our case several Asian wives in purdah, whose occupancy was almost total.

Air Pollutants, Radioactive↗

Antioxidants mimic the ability of chorionic gonadotropin to suppress apoptosis in the rabbit corpus luteum in vitro: a novel role for superoxide dismutase in regulating bax expression.

We have recently reported that members of the bcl-2 gene family are expressed and estradiol regulated in rabbit luteal cells during corpus luteum (CL) regression, and that estradiol and hCG are effective inhibitors of apoptosis in the rabbit CL in vivo and in vitro. As Bcl-2 and related proteins are known to regulate levels of reactive oxygen species or their intermediates in cells as one possible mechanism to control apoptosis, the present studies were designed to examine if oxidative stress plays a role in luteal cell apoptosis during CL regression in the rabbit. In the first set of experiments, healthy CL obtained from day 11 pseudopregnant rabbits were incubated in serum-free medium for 2 h in the absence or presence of superoxide dismutase (SOD; 1.5-150 U/ml), ascorbic acid (1-100 mM), N-acetyl-L-cysteine (25 and 50 mM), or catalase (10-1000 U/ml). Cells within CL incubated in medium alone exhibited extensive apoptosis (examined by analysis of extracted DNA using 3'-end labeling), and this onset of apoptosis was blocked in a dose-dependent fashion by treatment with SOD, ascorbic acid, N-acetyl-L-cysteine, or catalase. In the second set of experiments, expression of bax and bcl-x in CL after in vitro treatment without and with 100 U/ml SOD was examined. Although SOD treatment did not alter the levels of bcl-x messenger RNA (mRNA) over the 2-h incubation period, this antioxidant enzyme significantly reduced the levels of bax mRNA in incubated CL. In the final set of experiments, we observed that expression of mitochondrial- or manganese-containing SOD was significantly increased by treatment of isolated CL with 1 microg/ml hCG in vitro, whereas bax mRNA levels were significantly reduced under the same culture conditions. Collectively, these data indicate that the gonadotropin-mediated inhibition of apoptosis in rabbit luteal cells involves enhanced expression of the oxidative stress response gene, manganese-containing SOD, whose protein product may then function to protect luteal cells directly from the damaging effect of reactive oxygen species and/or indirectly by acutely down-regulating expression of Bax, a prooxidant member of the Bcl-2 protein family.

Animals↗

From housing to homes: a review of the literature on housing approaches for psychiatric consumer/survivors.

In this paper, we review the literature on housing for psychiatric consumer/survivors since the publication of the Nelson and Smith Fowler (1987) review more than a decade ago. First, we review research and propose a definition to contrast key features of three approaches to housing: (a) custodial, (b) supportive, and (c) supported. Second, we examine studies of the relationships between the characteristics of housing and adaptational outcomes for residents (e.g., personal empowerment). Third, we review studies which have examined out-comes for residents for these three different housing approaches. We conclude by critically reflecting on the values and research of the different approaches to housing, to make recommendations for future policy and planning, practice, and research.

Custodial Care↗

Evaluation of the impact of non-inpatient i.v. antibiotic treatment for acute infections on the hospital, primary care services and the patient.

The aim of this study was to assess the feasibility of providing i.v. antibiotic therapy outside hospital. The main outcome measures were the direct costs of providing i.v. antibiotic therapy in the community compared with standard hospital treatment and the perceptions of patients and General Practitioners (GPs). A total of 29 patients entered the study, of whom 15 received teicoplanin and 14 ceftriaxone. The costs of drugs exceeded the cost of the estimated alternative treatments (median Pound Sterling 208 and Pound Sterling 126 respectively) and this was only partially compensated for by a small reduction in costs of consumables. The staff time required to train patients was compensated for by savings in drug preparation and administration. Sensitivity analysis showed that these conclusions were sensitive to drug and patient selection, and that treatment of skin and soft tissue infections outside hospital with ceftriaxone was likely to have similar variable costs to treatment in hospital with drugs such as flucloxacillin. Non-inpatient i.v. (NIPIV) therapy was estimated to save a total of 532 bed days in the year of the study. Patients strongly preferred non-inpatient treatment to hospital treatment. GPs identified a number of potential disadvantages, mainly concerning safety and lack of support for patients at home. Following the study a strategy for development of NIPIV services in Tayside has been developed with local GPs and a plan has been agreed for funding a community liaison nurse based on the impact of NIPIV therapy on future bed requirements in Dundee Teaching Hospitals Trust.

Acute Disease↗

Short communication: estimates of radiation dose to National Health Service workers in Northamptonshire from raised radon levels.

Extensive surveys of the radon levels in hospital premises in Northamptonshire have shown that raised radon levels are present, but are localized to areas as small as a single office. Around 9% of sites are above the workplace action limit, and 1% of sites are over 1000 Bq m-3. In addition, radon levels vary throughout the day, and are usually higher at night. Staff in these areas could receive significant doses, and staff working shifts or at night could be at greater risk. Attempts to estimate staff dose using two methods are reported. It is concluded that, even though only a sample of the radon hot-spots was chosen, the radiation dose received by these staff is greater than the occupational exposure of radiographers, radiologists and other health workers.

Air Pollutants, Occupational↗

Flow and velocity waveform indices in the ovine fetal abdominal aorta with changes in behavioural state.

The purpose of this study was to determine the extent to which flow and velocity waveform indices are comparable as measured from the ovine fetal abdominal aorta and reflect downstream vascular resistance with changes in electrocortical activity. Nine chronically catheterized fetal sheep were studied near term with continuous measurement of electrocortical activity, perfusion pressure, and fetal heart rate. A cuffed Doppler crystal and a Transonic flow probe on the descending abdominal aorta were used for the simultaneous measurement of velocity waveforms and flow waveforms, with the Resistance Index (RI), calculated for each. Mean blood flow was also obtained from the Transonic flow probe. Whereas the change in cardiovascular parameters between the low- and high-voltage electrocortical activity (ECOG) states was small, with little relationship to the change in RI measurements, across all animals there was an inverse correlation between the RI measurements and fetal heart rate, perfusion pressure and aortic blood flow during both low- and high-voltage ECOG states. The RI as measured from the velocity waveforms showed only a modest correlation to those measured from the flow waveforms. It is concluded that over the range of circulatory change generated with spontaneous change in behavioural state, the RI as measured in the abdominal aorta of the ovine fetus is primarily determined by pulsatile cardiovascular variables rather than lower body vascular resistance.

Animals↗

Quantifying radiolabeled macromolecules and small molecules on a single gel.

A protein phosphorylation cascade involved in chemotactic signaling in Escherichia coli was investigated with purified components in vitro. CheA, an auto-phosphorylating histidine kinase, was mixed with [gamma-32P]ATP, and the labeled protein was purified for use as a reagent in the assays. CheY, a response regulator protein, can acquire phosphate groups from CheA but then undergoes rapid hydrolysis, which releases inorganic phosphate. To follow the kinetics of the CheA-CheY phospho-transfer reaction and the subsequent dephosphorylation of phospho-CheY, we separated the reaction components by polyacrylamide gel electrophoresis and measured the amount of 32P label in the CheA. CheY and inorganic phosphate bands with phosphor storage screens. By reducing the time needed to separate and quantify the reaction products, we minimized diffusive spreading of the low molecular weight inorganic phosphate, which enabled us to measure it accurately on the same gel with the much larger proteins. In principle, any radiolabeled molecules that can be separated by relatively rapid means, such as acrylamide gel electrophoresis, and that are detectable with a phosphor storage screen, should be amenable to this technique.

Adenosine Triphosphate↗

Purinergic stimulation of cell division and differentiation: mechanisms and pharmacological implications.

Extracellular purine nucleosides and nucleotides in micromolar concentrations stimulate proliferation of a variety of cell types in vitro and in vivo. As well they act synergistically with NGF to stimulate neurite outgrowth from PC12 cells. A variety of purine nucleosides and deoxyribonucleosides promote cell proliferation and increase intracellular cAMP. Their activities are inhibited by adenosine A2 receptor antagonists. Only adenosine interacts with the A2 receptor. We propose that the other nucleosides and deoxyribonucleosides inhibit extracellular adenosine deaminase, thereby increasing the extracellular concentration of adenosine. The nucleotides apparently act by stimulating P2y receptors coupled to inositol phosphate metabolism. We propose that the nucleosides and nucleotides act synergistically with other growth factors because each has distinct but complementary second messenger systems. If our hypotheses are correct, it should prove possible to modulate the growth and morphogenesis in several cell types using drugs that inhibit or stimulate adenosine A2 or purine P2y receptor agonists or the second messenger systems coupled to these receptors.

Animals↗

Prostacyclin inhibits mobilisation of fibrinogen-binding sites on human ADP- and thrombin-treated platelets.

Prostacyclin (prostaglandin I2, PGI2), produced by the blood vessel wall is the most potent known inhibitor of platelet aggregation induced by such stimuli as ADP and thrombin. It binds to a specific platelet receptor and activates adenylate cyclase, raising the cyclic AMP level in platelets. This property can be important because platelets participate in several significant interactions. For example, the interaction with fibrinogen or fibrin contributes to the formation of the haemostatic plug. Intact plasma fibrinogen is required for the aggregation of platelets induced by ADP, and endogenous platelet fibrinogen influences thrombin-induced aggregation. We have therefore studied the effect of prostacyclin on the interaction of fibrinogen with human platelets. We now report that prostacyclin inhibits the mobilisation of specific binding sites ('receptors') for fibrinogen on human platelets and that this effect parallels the inhibition of ADP- or thrombin-induced aggregation. The inhibitory effect of prostacyclin may limit the extent of platelet-fibrinogen interaction in vivo and in extracorporeal circulation.

Adenosine Diphosphate↗