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M Powell

Publications and source records attributed to M Powell.

At least 37 records · Page 2Linked to original sources
PubMed1998

Analysis of autoantibody epitopes on steroid 21-hydroxylase using a panel of monoclonal antibodies.

A panel of five mouse monoclonal antibodies (MAbs) to human recombinant steroid 21-hydroxylase (21-OH) were produced, characterized, and used to study the interaction of 21-OH autoantibodies (AAbs) with different epitopes on human 21-OH. AAbs in patients with isolated autoimmune Addison's disease, autoimmune polyglandular syndromes types I and II, and 21-OH antibody-positive patients without overt Addison's disease (25 patients in total) were studied. Four MAbs were IgG1 subclass, one was IgG2a, and all had kappa light chains. The affinities of four of the antibodies were in the range 2.0 x 10(8) M(-1) to 7.0 x 10(8) M(-1), and the affinity of the other was 2.3 x 10(7) M(-1) 21-OH MAbs did not cross-react with 17alpha-hydroxylase (17alpha-OH)) or P450 side chain cleavage enzyme. Studies using a series of 21-OH fragments allowed the identification of short stretches of amino acids (AA) that were involved in forming the MAb binding sites. AA 391-405, defined as epitope region (ER) 1, were found to be important for binding of M21-OH1 and M21-OH2, AA 406-411 (ER2) were important for M21-OH3 and M21-OH4 binding, and AA 335-339 (ER3) for M21-OH5 binding. In addition, MAb Fab or F(ab')2 fragments were used to study 21-OH AAb epitopes in competition experiments. These investigations demonstrated that 21-OH AAbs recognize similar epitopes to the MAbs, with ER2 and ER3 being part of two distinct major epitopes, and ER 1 being part of a minor epitope. Mixtures of M21-OH antibody Fab or F(ab')2 fragments caused almost complete inhibition (80%-95%) of AAb binding in 24 out of 25 sera, and in the case of the remaining serum, the effect was marked but incomplete (67% inhibition). There were no major differences between the binding characteristics of AAbs from patients with different forms of autoimmune adrenal disease. All five 21-OH MAbs reacted with human adrenal tissue in an immunofluorescence test, but only M21-OH1 and M21-OH2 reacted with bovine adrenal tissue in these experiments. None of the MAbs reacted with human ovarian tissue in an immunofluorescence test. Overall, these studies indicate that 21-OH AAbs bind to at least three different epitopes in the C-terminal part of 21-OH, and two of these epitopes appear to be human 21-OH specific.

Addison Disease↗
PubMed1997

The reticulocalbin gene maps to the WAGR region in human and to the Small eye Harwell deletion in mouse.

We describe the localization of the gene encoding reticulocalbin, a Ca2+-binding protein of the endoplasmic reticulum, on human chromosome 11p13 midway between the WT1 and the PAX6 genes and show that it is hemizygously deleted in WAGR individuals. The mouse reticulocalbin gene is also shown to map to the region of conserved synteny on mouse chromosome 2 and to be deleted in the Small eye Harwell (SeyH) mutation. Loss of the reticulocalbin gene could contribute to the early lethality of SeyH and SeyDey homozygotes.

Abnormalities, Multiple↗
PubMed1997

A placebo controlled study comparing the efficacy of intranasal azelastine and beclomethasone in the treatment of seasonal allergic rhinitis.

This study compared a new intranasal anti-allergic drug, azelastine (0.56 mg bid) with intranasal beclomethasone (0.2 mg bid) and placebo in the treatment of symptoms associated with seasonal rhinitis. After administering placebo for 3-5 days as a "run-in" period, eligible patients were randomized to treatment for 2 weeks: 83 patients received azelastine, 83 beclomethasone and 77 placebo. Each of six symptoms was assessed daily using a four-point scale. Total symptom scores showed that azelastine-treated patients experienced a more rapid onset of overall symptom relief than beclomethasone-treated patients. This was significant on day 1 (P < 0.003) and continued until day 5. By the end of the 2-week study period, the beclomethasone-treated group showed greater improvement than both the azelastine and placebo groups (P = 0.002 and P = 0.0001, respectively). In contrast, visual analogue scales at this time showed no significant differences between the azelastine and beclomethasone treatment groups, with both groups demonstrating significant reductions in total symptom scores compared to placebo (P = 0.0004 and P = 0.0001, respectively). Differing sensitivities were found in the four-point scales reported by the patients and the investigators and the patients' visual analogue scales in the measurement of symptom severity. However, all three techniques confirmed that both azelastine nasal spray and beclomethasone nasal spray were effective treatments for seasonal rhinitis. While a greater improvement in overall symptoms was found for the beclamethasone-treated patients compared to azelastine-treated patients, diary card data confirmed the more immediate onset of symptom relief provided by azelastine. No serious adverse events were found in the present study and included no complaints of drowsiness.

Administration, Intranasal↗
PubMed1997

Socialism and the British National Health Service.

This paper examines some of the key characteristics of a socialist health care system using the example of the British National Health Service (NHS). It has been claimed that the NHS has socialist principles, and represents an island of socialism in a capitalist sea. However, using historical analysis, this paper argues that while the NHS claims some socialist ends, they could never be fully achieved because of the lack of socialist means. The socialist mechanisms which were associated with earlier plans for a national health service such as salaried service, health centres, elected health authorities and divorcing private practice from the public service were discarded in negotiation. Moreover, even these would have achieved socialism merely in the sense of distributing health care, without any deeper transformation associated with doctor-patient relationships and prevention. In short, the NHS is more correctly seen as nationalised rather than socialised medicine, achieving the first three levels of a socialist health service identified here. It can be said to have socialist principles in the limited distributional sense and has some socialist means to achieve these. However, it lacks the stronger means to fully achieve its distributional goals, and is very distant from the third level of a radical transformation of health care.

England↗
PubMed1997

Sellar tuberculoma: report of two cases.

Hypophyseal tuberculomas are exceptionally rare. We report two patients with sellar tuberculoma but with no evidence of concurrent extrasellar disease. Although the lesion is often mistaken for adenoma, there are characteristic radiological features: intense enhancement on contrast CT and thickening of the pituitary stalk on MRI in 86% of cases. Accurate diagnosis is important because pituitary tuberculoma is curable.

Adult↗
PubMed1997

Management of blunt splenic trauma: significant differences between adults and children.

BACKGROUND: Although highly successful in children, nonoperative management of blunt splenic injury in adults is less defined. The purpose of this study was to determine whether mechanism of injury, grade of splenic injury, associated injuries, and pattern of injury differ between adults and children (younger than 15 years of age). METHODS: Four hundred eleven patients (293 adults and 118 pediatric patients) with blunt splenic injury were admitted to an affiliated adult/pediatric trauma program from 1989 to 1994. Computed tomography (CT) scans were interpreted in a blinded fashion. Mechanism of injury was significantly different for adults versus children (p < 0.05): motor vehicle crash (66.9% versus 23.7%), motorcycle (8.8% versus 0.8%), sports (2.4% versus 16.9%), falls (8.8% versus 25.4%), pedestrian/automobile (4.4% versus 11.0%), bicycle (1.4% versus 9.3%), and other (7.3% versus 12.7%). RESULTS: Higher injury severity scores, lower Glasgow Coma Scales, and higher mortality indicated that the adults were more severely injured than the children. Fifty-nine percent of the adults and 7% of the children required immediate laparotomy for splenic injury. Both CT grade and quantity of blood on CT predicted the need for exploration in adults but not in children. An injury severity score above 15 and high-energy mechanisms correlated with the need for operative intervention. CONCLUSIONS: Rather than children simply being physically different, they are injured differently than adults, hence the high rate of nonoperative management.

Accidents, Traffic↗
PubMed1997

Transsphenoidal surgery for pituitary tumours.

OBJECTIVES: Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children. STUDY DESIGN: A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre. RESULTS: Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS. CONCLUSIONS: TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients.

Adenoma↗
PubMed1997

Steroid 21-hydroxylase autoantibodies: measurements with a new immunoprecipitation assay.

Autoantibodies (Abs) to steroid 21-hydroxylase (21-OH) are a major component of adrenal cortex Abs and are characteristic of autoimmune Addison's disease. We have developed a new method for measuring Abs to 21-OH based on 125I-labeled recombinant human 21-OH produced in yeast. With this assay, 21-OH Abs were detected in 43 of 60 (72%) sera from patients with isolated Addison's disease, 11 of 12 (92%) autoimmune polyglandular syndrome type I sera, 27 of 27 (100%) autoimmune polyglandular syndrome type II sera, and 24 of 30 (80%) sera from patients who were positive for adrenal cortex antibodies by immunofluorescence but had no overt Addison's disease. 21-OH Abs were found by 125I assay in 4 of 150 (2.7%) sera from patients with insulin-dependent diabetes mellitus, 1 of 77 (1.3%) Graves' sera, 1 of 67 (1.5%) Hashimoto's sera, and 6 of 243 (2.5%) sera from healthy blood donors. 21-OH Abs were not detected in 9 sera from patients with Addison's disease due to tuberculosis, 32 sera from patients with noninsulin-dependent diabetes mellitus, 35 sera from patients with myasthenia gravis, or 17 sera from patients with premature ovarian failure. There was good agreement between the 125I-labeled 21-OH assay and an assay based on 35S-labeled 21-OH produced in an in vitro transcription/translation system (r = 0.86; n = 129; P < 0.001). In the case of sera from patients with Addison's disease, insulin-dependent diabetes mellitus, Graves' disease, and Hashimoto's disease and from healthy blood donors that were low positive in the 125I assay, neutralization studies with unlabeled 21-OH confirmed the presence of specific 21-OH Abs. Overall, the 21-OH Ab assay based on 125I-labeled 21-OH showed good sensitivity, precision, and disease group specificity. This, combined with a simple assay protocol and the convenience of 125I handling and counting, make it attractive for routine use. Further investigations with the new assay should allow wider assessment of the prevalence and pattern of inheritance of adrenal autoimmunity. In addition, studies of the effect of treatment or possible preventative measures on 21-OH Ab levels in individuals without overt adrenal failure may suggest ways of delaying the onset of autoimmune Addison's disease.

Addison Disease↗
PubMed1997

Reliability of continuous tracer infusion for measuring glucose turnover rate in rainbow trout

Glucose plays a fundamental role in mammalian energetics but its contribution as a metabolic fuel is not well established for fish; the accurate in vivo measurement of glucose flux is essential to determine the importance of this substrate in the energy budget of teleosts. Therefore, the goal of the present study was to verify the reliability of the continuous tracer infusion method for estimating glucose turnover rate in rainbow trout Oncorhynchus mykiss. Our secondary goals were to determine whether glucose flux can be estimated more accurately from plasma or from whole-blood samples, and to obtain an estimate of renal glucose production. Continuous infusions of [6-3H]glucose were performed in hepatectomized and intact animals. In some hepatectomized individuals, liver glucose production was replaced by a pump infusing unlabelled glucose at a known rate. Renal glucose production was measured in hepatectomized fish where liver glucose production was not replaced, and it averaged 1.1&plusmn;0.1&micro;molkg-1min-1 (mean &plusmn; s.e.m., N=5). Results show that glucose turnover rate is quantified accurately by continuous tracer infusion and that glucose flux can be estimated equally well from plasma (error of -0.7&plusmn;4.9%) and from whole-blood (error of -5.7&plusmn;2.9%) samples (means &plusmn; s.e.m., N=7). This study provides the first experimental validation of continuous tracer infusion in fish, and shows that this method could become a powerful tool to investigate hormonal regulation of glucose metabolism in live teleosts.

Journal Article↗
PubMed1997

Autoantibody binding to steroid 21-hydroxylase--effect of five mutations.

Steroid 21-hydroxylase (21-OH) is a key haem containing steroidogenic enzyme and a major adrenal specific autoantigen. Cys 428 in 21-OH is thought to have an important role in haem binding and we now describe the effects of mutations at Cys 428 (to Ser, Arg and Phe) on 21-OH autoantibody binding. Expression of wild type and mutated 21-OH was carried out using an in vitro transcription/translation (TnT) system and reactivity of 21-OH autoantibodies with mutated 21-OH analysed by western blotting (in the case of unlabelled proteins) or immunoprecipitation assay (IPA) (in the case of 35S-labelled proteins). All 3 substitutions at Cys 428 had similar effects on 21-OH autoantibody binding and each one caused a reduction in autoantibody binding to about 50% of wild type in the case of IPA and to about 70% of wild type in the case of western blotting analysis. In addition to mutations at Cys 428, we studied 2 naturally occurring mutations at Pro 30 to Leu and Ile 172 to Asn which are associated with diminished 21-OH enzyme activity. The Pro 30 mutation had no effect, but the Ile 172 mutation caused a reduction in 21-OH autoantibody binding in the IPA to about 80% of wild type. Overall, our studies emphasise the close relationship between the 21-OH aminoacid sequences important for 21-OH enzyme activity and 21-OH autoantibody binding.

Addison Disease↗
PubMed1997

Venturi vacuum systems for hypobaric chamber operations.

Physiological studies of the effects of high altitude on man often require the use of a hypobaric chamber to simulate the reduced ambient pressures. Typical "altitude" chambers in use today require complex mechanical vacuum systems to evacuate the chamber air, either directly or via reservoir system. Use of these pumps adds to the cost of both chamber procurement and maintenance, and service of these pumps requires trained support personnel and regular upkeep. In this report we describe use of venturi vacuum pumps to perform the function of mechanical vacuum pumps for human and experimental altitude chamber operations. Advantages of the venturi pumps include their relatively low procurement cost, small size and light weight, ease of installation and plumbing, lack of moving parts, and independence from electrical power sources, fossil fuels and lubricants. Conversion of three hyperbaric chambers to combined hyper/hypobaric use is described.

Altitude↗
PubMed1997

Cloning, characterization and identification of the gene encoding phosphatidylinositol 4-kinase.

The vast majority of AIDS-related deaths are associated with opportunistic infections. For fungal infections, there are few effective antifungals, particularly for systemic use. The discovery that very low doses of the bleomycin family of anticancer chemical congeners compromise the integrity of fungal cell walls led to our approach to identify genes that complement-cell wall defects, and develop methods to facilitate the identification of new antifungals targeted to fungal cell walls. This report describes one of the genes cloned by complementation of the blm1-1 mutation of S. cerevisiae using a YCp50-based yeast genomic library. Characterization and identification of the gene were carried out using drug screening tests, Southern hybridization analyses, DNA sequencing and DNA sequence similarity searches in databases. The gene STT4, is essential for viability and encodes a phosphatidylinositol 4-kinase that plays an important role in the phosphatidylinositol-mediated signal transduction pathway required for cell wall integrity. Like blm1-1 mutant strains, stt4 cells arrest mostly in the G2/M phase of the cell cycle. Further studies using this approach should help us understand the role of PI4-K in maintaining fungal cell-wall integrity, identify additional genes affecting potential target structures in cell walls of opportunistic fungal pathogens in AIDS patients, and assist in drug discovery and antifungal drug design.

1-Phosphatidylinositol 4-Kinase↗
PubMed1996

Glutamic acid decarboxylase autoantibody assay using 125I-labelled recombinant GAD65 produced in yeast.

We describe a new method for measuring autoantibodies (Ab) to the 65 kDa isoform of glutamic acid carboxylase (GAD65). In particular, GAD65 without the hydrophobic N-terminal region has been produced in yeast, purified, labelled with 125I and reacted with GAD65 Ab. Antibody bound 125I-GAD65 is then precipitated by the addition of solid phase protein A. With the assay, GAD65 Ab were detected in 59 of 71 (83%) islet cell antibody (ICA) positive IDDM patients and in 8 of 23 (35%) ICA negative IDDM patients (overall 67 of 94 (71%) of IDDM patients). Low concentrations of GAD65 Ab were also detected in 2/98 (2%) healthy blood donors and 1/27 (4%) Graves' disease patients had a high level of antibody. GAD65 Ab were not detected in any of 10 Hashimoto's thyroiditis, 20 Addison's disease or 19 myasthenia gravis sera. There was good agreement between the 125I assay and the current reference method based on 35S-labelled full-length GAD65 (produced by in vitro transcription/translation reaction) and solid phase protein A (r = 0.91, n = 108). Overall, our 125I assay showed sensitivity, precision and disease group specificity at least as good as any assay so far described. These features, combined with a simple assay protocol and the convenience of 125I counting and handling indicate that the method is suitable for routine GAD65 Ab measurements.

Adult↗
PubMed1996

Biocompatible osteoconductive polymer versus iliac graft. A prospective comparative study for the evaluation of fusion pattern after anterior cervical discectomy.

STUDY DESIGN: One hundred fifteen patients having symptomatic cervical disc disease were recruited prospectively for this study. They were allocated randomly for either autologous iliac bone graft or biocompatible osteoconductive polymer implants. Both groups were compared clinically and radiologically. OBJECTIVES: Complications, long-term clinical and radiologic outcome, and hospital stay were compared to determine if biocompatible osteoconductive polymer was an improvement on iliac bone graft in terms of reduced donor site pain and shortened hospital stay. SUMMARY OF BACKGROUND DATA: Donor site morbidity is a significant problem in anterior cervical fusion. Hospital stay is another factor in the recent era of cost consciousness. Biocompatible osteoconductive polymer has been used in many centers as a biodegradable implant to circumvent these problems. METHODS: Smith-Robinson technique was used in 74 patients, and Cloward technique was used in 41 patients. Sixty-five patients had biocompatible osteoconductive polymer implants, and 50 patients had iliac bone graft. Patients were followed-up routinely in the outpatient clinic where pain visual analogue scale and Odom's criteria were used for outcome evaluation. Plain radiography, computed tomography scan, and magnetic resonance imaging were used for radiologic evaluation. RESULTS: The mean hospital stay was 4.8 days for those with iliac bone graft and 4.7 days for those with biocompatible osteoconductive polymer. Clinical outcome was identical in both groups. The incidence of partial graft protrusion and postoperative intersegmental kyphosis was statistically higher with iliac bone graft (P = 0.018 and P = 0.02, respectively). "Sclerosis" started to form around biocompatible osteoconductive polymer like a "halo" at 2 months. It increased with time, and sometimes was associated with new osteophyte formation; however, there was no biocompatible osteoconductive polymer incorporation or biodegradation CONCLUSIONS: Biocompatible osteoconductive polymer acts as a good "spacer" that reduces graft collapse and intersegmental kyphosis. However, it did not show any radiologic evidence of biodegradation or incorporation during the follow-up period of 24 months.

Adult↗
PubMed1996

The development of independent practice associations and related groups in New Zealand.

AIMS: Independent practice associations (IPAs) have become an important feature of New Zealand's primary care system in the past two years and now represent nearly 60% of general practitioners. This survey was undertaken to document this important development. To determine the extent of the development of IPAs, their goals and barriers to achieving these goals, their policies, financing and contracting development. METHODS: Questionnaire sent to 42 IPAs and related groups in October 1994 with a supplementary questionnaire in April 1995. RESULTS: There were 34 responses, representing the views of 1263 general practitioners. Most important goals were "achieving better health outcomes for patients", "making better use of primary care resources" and "improving the health of the community you serve". Significant barriers to achieving these goals were "lack of time" and "lack of clear RHA policies". There was little support for financial risk sharing or for members personally retaining savings from budget holding. Although there had been significant progress with budget holding considerable frustration was expressed about contracting relationships with RHAs. CONCLUSION: The survey shows that general practitioners are seeing IPAs as ways of achieving professional goals, better quality health care and improving health status outcomes rather than as a means of personal gain. However, protecting and advancing the status of general practice was also important. IPAs expect to move progressively into both budget holding and managed care with the gradual assumption of secondary care services purchasing. This has important implications for the future of RHAs including the need for them to adopt a more strategic purchasing role.

Attitude of Health Personnel↗
PubMed1996

Prospective study of safety of lower extremity phlebography with nonionic contrast medium.

BACKGROUND: Lower extremity deep venous thrombosis (DVT) following hig h osmolar ionic contrast phlebography has been reported to vary between 9% to 31%. The purpose of this study was to determine the incidence of minor and major adverse reactions and postphlebographic DVT when using nonionic contrast (iopamidol). PATIENTS AND METHODS: One hundred fifty-seven patients with clinically suspected DVT were studied prospectively. One hundred eleven patients had prephlebography duplex ultrasound, and 102 patients were examined in the vascular laboratory for delayed side effects 1 week after phlebography. The presence of phlebography induced DVT was assessed using color duplex ultrasound. The mean amount of contrast used 102 ml. RESULTS: Minor adverse reasons, including nausea, local pain, and dizziness, occurred in 11 (7%) of 157 patients; however, no major complications or postphlebographic DVT was found in the 102 patients who underwent postphlebography duplex ultrasound. Phlebography and pre- and postphlebography duplex ultrasound showed no acute DVT in 70 patients. The maximum hypothetical true rate of major complications (ie, postphlebography DVT) that would result in no detectable events in a population of 102 patients with follow-up (for a probability of P <0.05) is 2.9. CONCLUSION: lower extremity phlebography using nonionic contrast material is safe, with no incidence of postphlebography DVT in our series. Its utilization should be encouraged if duplex ultrasound is not available.

Adolescent↗