Search PubMed⌕ Search

Biomedical subjects

S Goodwin

Publications and source records attributed to S Goodwin.

At least 19 recordsLinked to original sources
PubMed2006

Effective treatment of an elderly patient with Gaucher's disease and Parkinsonism: a case report of 24 months' oral substrate reduction therapy with miglustat.

We report here the results of 24 months' treatment with oral miglustat of a patient with mild-to-moderate Gaucher's disease (GD) and Parkinsonism. The patient's progressive Parkinsonian tremor, in addition to restricted vascular access, necessitated switching treatment for GD from intravenously infused enzyme replacement therapy (ERT) that had been administered for the previous 7 years. With control of haematological parameters and markers of GD activity improved or maintained and no notable adverse effects, miglustat treatment proved an effective and well-tolerated therapeutic alternative to ERT. Oral miglustat should be considered for the treatment of patients with type I GD and concurrent movement disorders who are unsuitable for ERT.

1-Deoxynojirimycin↗
PubMed2005

Developing the public health practitioner workforce in England: lessons from theory and practice.

FOCUS: The paper focuses on public health practitioners who collectively represent one of three key workforce groups identified by England's Chief Medical Officer as critical to the successful delivery of national public health policy priorities. QUESTION: We report on two areas of work which attempt to address the following two-part question: in developing the public health practitioner workforce in England, what is needed, and how do we do it? APPROACH: First, we describe a five-component conceptual framework for developing the public health workforce which is grounded in data derived from a national Open Space event hosted by the University of the West of England in March 2005. The five components are (i) strategic support and oversight; (ii) national technical and professional support; (iii) national career building; (iv) local organisational development, and (v) sub-regional skills development. Key elements of each component are described in the paper. Second, we describe in some detail a new multidisciplinary skills development programme which illustrates one of the framework components (sub-regional skills development). The programme, established in January 2005, is aimed at three key groups of public health practitioners: health visitors (specialist community public health nurse), school nurses and environmental health officers. Its main features and some initial evaluation findings are presented. CONCLUSIONS: To be effective, activities aimed at supporting the development of the public health practitioner workforce should, where possible, aim to be congruent with core public health principles of self-determination and collective responsibility. We also conclude that leadership and vision at a national level, combined with local implementation of evidence-based training programme such as the one described could help to achieve much greater and more rapid progress in skilling up the existing public health practitioner workforce than has been possible up to now. But we note that this requires sustained investment, robust sector-wide delivery frameworks, and a group of committed local public health champions.

Humans↗
PubMed2005

A comparison between the theory and reality of full-scale step-feed nutrient removal systems.

Capacity enhancement and volume reduction benefits of step-feeding fully aerobic bioreactors has been well documented. Application of step-feed technology to biological nutrient removal (BNR) systems, particularly those removing nitrogen alone or both nitrogen and phosphorus, is relatively new to the industry. In recent years, a number of full-scale step-feed facilities have been brought into service. This paper reviews nine full-scale step-feed biological nutrient removal systems--both nitrogen removal alone, and nitrogen and phosphorus removal. The objective is to compare the theoretical benefits of such systems with their actual operation. The predicted benefits of reduced bioreactor volume or increased process capacity, reduced energy usage, more robust nitrification performance, and the flexibility to tune (or de-tune) nitrification efficiency were verified in full-scale systems. Equations are also presented that may be used in the prediction of step-feed benefits. There are two primary drivers for considering a step-feed biological reactor system: 1. Reduced bioreactor volume for a defined capacity or performance or increased process capacity given a fixed bioreactor volume. 2. More robust nitrification performance. Full-scale operation of these step-feed nutrient removal systems provides a real world basis for the claimed benefits of step-feed operation. These systems have uniformly shown additional capacity. A number of them have also exhibited more robust performance, especially during storms. Where possible, side-by-side comparisons of full-scale step-feed systems with non-step-feed systems have exhibited greater process reliability and flexibility.

Bioreactors↗
PubMed2004

Primary B-cell lymphoma of the skin: the Sheffield Lymphoma Group Experience (1984-2003).

The clinical presentation, treatment and outcome were retrospectively evaluated in a series of 66 patients with primary B-cell lymphoma of the skin, referred to the Sheffield lymphoma group (SLG) between 1984 and 2003. This is the largest series reported from the UK. The lymphoma database was searched and clinical records were reviewed. Absence of any detectable extracutaneous lesion and the expression of B-cell restricted antigens by neoplastic cells were the essential criteria for selection of cases. The cohort included 37 (56%) males and 29 (44%) females with a mean age of 59 years. The most commonly involved site was the trunk and the disorder typically showed non-aggressive clinical behaviour; the majority of the patients presented with stage I (82%) disease with a tendency to remain localised to a limited area of the skin. Follicular lymphoma was the most common histologic subtype (35%), the next most frequent was the diffuse large cell lymphoma (32%) whereas marginal zone lymphoma constituted 15%. The majority (47%) of patients were treated with radiotherapy for localised disease whereas chemotherapy was given in 20% of patients, with single agent chlorambucil being most frequently used. Surgical excision as the sole modality of treatment was adequate in 33%. Disease-free survival (DFS) was 91% at 1 year, 82% at 2 years and 60% at 5 years. DFS was significantly lower with older age (>45 years), leg lesions, generalised and multiple lesions, and for those treated with chemotherapy. The survival at 5 and 10 years was 80%. The histologic grade, leg involvement and the number of lesions were the most significant variables affecting overall survival. Only 7 patients died of lymphoma. In conclusion, primary cutaneous B-cell lymphoma represents a specific entity concerning clinical behaviour, response to treatment, and overall prognosis.

Adolescent↗
PubMed2003

Hearing improvement in patients with Fabry disease treated with agalsidase alfa.

AIM: To describe the nature and prevalence of hearing loss in Fabry disease, and its response to enzyme replacement therapy (ERT) with agalsidase alfa. METHODS: Fifteen male patients with Fabry disease were enrolled in a randomized, double-blind study and received placebo (n = 8) or ERT (n = 7) with agalsidase alfa for 6 months. This was followed by an open-label extension of 36 months thus far. Alongside this trial, an additional eight men and two women have so far received open-label ERT for between 6 and 30 months. Pure-tone audiometry, impedance audiometry and otoacoustic emission testing were performed at 0 (baseline), 6, 18, 30 and 42 months. RESULTS: Nine patients (36%) had bilateral and ten (40%) had unilateral high-frequency sensorineural hearing loss (SNHL). Three (12%) had unilateral middle ear effusions with conductive losses persisting beyond 6 months. Only five patients (20%) had normal hearing. The high-frequency SNHL deteriorated over the first 6 months in both placebo and active treatment groups by a median 6.3 dB (p < 0.0001, Wilcoxon matched-pairs). This hearing loss subsequently improved above baseline by 1.5 dB at 18 months (p = 0.07), by 5.0 dB at 30 months (p = 0.006) and by 4.0 dB at 42 months (p = 0.01). CONCLUSION: Significant hearing loss, usually high-frequency SNHL, is a common manifestation of Fabry disease in adults. Alpha-galactosidase A replacement therapy with agalsidase alfa appears to reverse the hearing deterioration in these patients. This improvement, however, is gradual, suggesting the need for long-term ERT.

Adolescent↗
PubMed2002

Outcomes following unilateral uterine artery embolisation.

Uterine artery embolisation has been described as successful only when both arteries are embolised. However, results in patients with one congenitally absent or previously ligated artery are unknown. Women suffering from symptomatic uterine myomata were treated at a university teaching hospital, a community hospital and an outpatient surgery centre. Retrospective review of patient response to embolisation was assessed by chart review and questionnaire. Uterine and dominant fibroid size response was assessed by comparing pre- and post-embolisation ultrasound examinations. This study analysed three patient groups within the general population: those who underwent unilateral embolisation because of technical failure, those who ultimately underwent bilateral embolisation after initial technical failure and those who underwent unilateral embolisation because of an absent uterine artery. 12 patients underwent unilateral embolisation, 4 of whom underwent this procedure because of an absent uterine artery. Three of these four patients had a congenitally absent uterine artery arising from the internal iliac artery and all three experienced successful outcomes. The fourth patient had a previously ligated internal iliac artery and her symptoms worsened after the procedure. Eight patients had unilateral embolisation due to technical failure. Five of these patients underwent a subsequent procedure during which the contralateral uterine artery was embolised. Four of these five patients had successful outcomes and one was lost to follow-up. Another of the eight patients suffered an arterial injury leading to technical failure, and was lost to follow-up. Of the two remaining patients with unilateral technical failure, only one had a successful outcome. This study concluded that patients who undergo unilateral embolisation for technical reasons should be offered a second embolisation procedure shortly after the initial procedure. Patients with a congenitally absent uterine artery may respond with similar success to those who underwent bilateral embolisation. In contrast, the patient with a previously ligated internal iliac artery failed. The numbers in this study are too small for statistical analysis and subsequent studies should be performed to confirm these findings.

Angiography↗
PubMed2001

Comparative study of the relationship between monomer structure and reactivity for two polyhydroxyalkanoate synthases.

Using organically synthesized hydroxyalkanoate coenzyme A thioesters, the activities of two short-chain polyhydroxalkanoate (PHA) synthases were investigated--Ralstonia eutropha PHA synthase (a type I PHA synthase) and Ectothiorhodospira shaposhnikovii PHA synthase (a type III synthase). The results indicate that the two synthases have similar activities towards most of the monomers tested. 3-Hydroxybutyryl CoA was found to be the most efficient substrate for both synthases. Changes in the side-chain length of the monomers affect monomer reactivity, with shortening of the side-chain length having the more severe effect. Hydrophobicity in the side chain appears to play an important role in the catalytic reaction. The configuration and the position of the hydroxyl group also affect the reactivity of a monomer. Monomers with the [S] configuration can not be recognized by either synthase. Moving the hydroxyl group from the beta carbon to the alpha carbon has a much more severe effect on the reactivity of the monomer than moving the hydroxyl group to the gamma carbon. The results demonstrate that the in vitro system can be used to prepare entirely novel polymers that may not be obtainable from living cells because of metabolic restrictions.

Acyl Coenzyme A↗
PubMed2001

Pregnancy following uterine fibroid embolization.

OBJECTIVE: This paper seeks to evaluate the ability to deliver term pregnancies following uterine fibroid embolization, and to identify impediments to pregnancy in the embolization procedure. STUDY DESIGN: Four physicians performed embolization procedures at various facilities. Patients were asked if fertility was an issue prior to embolization. We measured follicle-stimulating hormone levels before and after embolization. Clinical follow-up, six months following embolization was obtained by interview. Patients were questioned regarding attempts to conceive, menstrual history, and subsequent pregnancy. MAIN OUTCOME MEASURES: Complications were calculated upon the entire patient population, whether or not fertility was identified as a goal. Fertility risks from embolization were identified. We measured radiation exposure in a random consecutive group of 50 women undergoing embolization. All patients who conceived were asked the details of the pregnancy. RESULTS: Four hundred women underwent uterine fibroid embolization between 1996 and 1999. One hundred and thirty nine patients stated a desire for fertility after embolization. Of these, 52 were <40 years old. Seventeen pregnancies have been reported in 14 women. Five spontaneous abortions were observed. Ten women have had normal term deliveries and two women are currently pregnant. No perfusion problems, either during the pregnancy or labor, were reported. The average radiation dosage calculated for 50 women undergoing embolization was 14 rads. Four women under 45 years old suffered premature menopause (10/1000). Two women underwent hysterectomy as a complication of embolization (5/1000). CONCLUSION: The risks of infertility following embolization, premature menopause, and hysterectomy are small, as is the radiation exposure during embolization. These risks compare favorably with those associated with myomectomy. Fertility rates appear similar to patients undergoing myomectomy. No problems, either during pregnancy or delivery, have been observed after embolization. The course of pregnancy and delivery was normal after embolization with no maternal or fetal complications reported. These findings confirm results from other centers. Desire for future pregnancy is not a contraindication to fibroid embolization.

Abortion, Spontaneous↗
PubMed2001

Neurobiology.

Explore the source record for details and available documents.

Journal Article↗
PubMed2001

Neurobiology.

Explore the source record for details and available documents.

Animals↗
PubMed2001

Bleeding complications associated with the use of rt-PA versus r-PA for peripheral arterial and venous thromboembolic occlusions.

This article analyzes the early experience with alteplase (rt-PA) and reteplase (r-PA) to identify noteworthy differences in bleeding and to determine correlations with dosage, concomitant anticoagulation, and duration of infusion. A retrospective review of the medical records was unavailable for the initial 82 patients who were treated with either rt-PA (44) or r-PA (38) for peripheral arterial or venous occlusions after urokinase therapy. Successful recanalization was achieved in 31/44 (70%) of the patients treated with rt-PA and in 34/38 (89%) of the patients treated with r-PA. Significant bleeding was documented in 20/44 (45%) of the rt-PA-treated patients (including 14 transfusions) versus 3/38 (8%) of the r-PA-treated patients (3 transfusions). Concomitant anticoagulation with either preceding warfarin (international normalized ratio > 1.1) or a bolus of heparin at the outset of the infusion was associated with significant bleeding in 13/17 (76%) of the rt-PA-treated patients (including 9 transfusions) versus 0/17 in the r-PA-treated patients. No significant correlation between either mean dose or total dose and bleeding was shown for either drug. Early experience indicates that r-PA is at least as effective as rt-PA for the thrombolysis of peripheral arterial and venous occlusions. It also appears that r-PA is less likely than rt-PA to be associated with significant bleeding during such infusions, especially if the patient is concomitantly anticoagulated.

Adolescent↗
PubMed2000

Enzymatic hydrolysis of oligomeric models of poly-3-hydroxybutyrate.

The mechanism of the enzymatic degradation of poly([R]-3-hydroxybutyrate) (PHB) was investigated by using well-defined model substrates, including both linear and cyclic [R]-3-hydroxybutyrate (3HB) and [R]-3-hydroxyvalerate (3HV) oligomers, with two different PHB depolymerases. The linear and cyclic oligomers containing from 2 to 10 repeating units were hydrolyzed in solutions of the depolymerase isolated from Aspergillus fumigatus and Alcaligenes faecalis, and the rates of hydrolysis and types of products formed were characterized. Both of the depolymerases catalyzed the hydrolysis of the cyclic oligomers (macrolides) which contained more than three 3HB and 3HV repeating units. The degradation reactions of the linear and cyclic 3HB oligomers with the A. fumigatus depolymerase gave similar ratios of monomer-to-dimer products, but PHB itself formed mostly monomer on hydrolysis, indicating that the enzymatic hydrolysis reactions occurred by different mechanisms for these different types of substrates. The results of this study conclusively show that at least the endo mode of polymer hydrolysis occurs with the two enzymes studied, while the A. fumigatus depolymerase was found to utilize both endo and exo modes of hydrolysis to efficiently degrade PHB and 3HB oligomers.

3-Hydroxybutyric Acid↗
PubMed2000

Kinetic and mechanistic characterization of the polyhydroxybutyrate synthase from Ralstonia eutropha.

Purified Ralstonia eutropha polyhydroxybutyrate (PHB) synthase from recombinant cells can exist as monomer and dimer. The polymerization reaction catalyzed by this enzyme displays a lag phase, which causes difficulties for kinetic and mechanistic characterization of the enzymatic polymerization reaction. In this study, we developed a method to eliminate the lag phase of PHB synthase by physical means, i.e., adding multihydroxyl compounds to the enzyme solution. This method allows us to recognize the nature of the lag phase as a physical rather than a chemical process. With such lag-phase-free-enzyme, the kinetic properties of the enzyme were investigated. The results indicate that 3-hydroxybutyryl-CoA (3HBCoA) is the optimal substrate for the enzyme. A slower catalytic rate and lower binding ability account for a lower reactivity of 3-hydroxyvaleryl-CoA (3HVCoA) compared to that of 3HBCoA. The change of hydroxyl group from the beta to the gamma position causes dramatic decreases in the binding ability of 4-hydroxybutyryl-CoA (4HBCoA). By using a dilution strategy and size exclusion chromatographic technique, the active form of the enzyme was identified to be the dimeric form. The number of catalytic sites in the dimeric form of the enzyme was examined by comparing the molecular weight of polyhydroxybutyrate as a function of substrate-to-enzyme ratio. The results suggest that the dimeric enzyme has only one catalytic site. A revised model of polymerization reaction catalyzed by R. eutropha PHB synthase is described.

Acyltransferases↗
PubMed2000

In vitro polymerization and copolymerization of 3-hydroxypropionyl-CoA with the PHB synthase from Ralstonia eutropha.

The poly(3-hydroxybutyrate) (PHB) synthase of Ralstonia eutropha, which was produced by a recombinant strain of Escherichia coli and purified in one step with a methyl-HIC column to a purity of more than 90%, was used to polymerize 3-hydroxypropionyl-CoA (3HPCoA) and to copolymerize 3HPCoA with 3-hydroxybutyryl-CoA (3HBCoA). A Km of 189 microM and a kcat of 10 s-1 were determined for the activity of the enzyme in the polymerization reaction of 3HPCoA based on the assumption that the dimer form of PHB synthase was the active form. Free coenzyme A was found to be a very effective competitive inhibitor for the polymerization of 3HPCoA with a Ki of 85 microM. The maximum degree of conversion of 3HPCoA to polymer was less than 40%. In the simultaneous copolymerization reactions of these two monomers, both the turnover number for the copolymerization reaction and the maximum degree of conversion of 3HPCoA and 3HBCoA to copolymers increased with an increase in the amount of 3HBCoA in the monomer mixture. However, the maximum conversion of 3HPCoA to copolymer was always less than 35%, regardless of the ratio of 3HPCoA to 3HBCoA. Block copolymers were obtained by the sequential copolymerization of the two monomers and these copolymers had a much narrower molecular weight distribution than those obtained by the simultaneous copolymerization for the same molar ratio of 3HPCoA to 3HBCoA.

Acyltransferases↗
PubMed2000

Down-regulation of TGF-beta1 production restores immunogenicity in prostate cancer cells.

The objective of this study is to determine if a non-immunogenic Dunning's rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-beta1. An expression construct containing a DNA sequence in an antisense orientation to TGF-beta1 (TGF-beta1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-beta1 reduced from 70 to 10 pg per 2x10(4) cells and the rate of in vitro 3H-thymidine incorporation increased 3-5-fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, P< or =0.05) for cells transfected with TGF-beta1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-beta1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-beta1 is down-regulated.

Animals↗