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Biomedical subjects

M Powell

Publications and source records attributed to M Powell.

At least 19 recordsLinked to original sources

Autoantibodies to IA-2 in insulin-dependent diabetes mellitus. Measurements with a new immunoprecipitation assay.

An immunoprecipitation assay for autoantibodies (Abs) to the human islet cell antigen IA-2 has been developed using 125I-labelled recombinant IA-2 expressed in E. coli. With this assay IA-2 Abs were detected in 103/217 (47%) of IDDM patients of different ages and with different disease duration. IA-2 Ab prevalence was higher in younger patients (at the age of 15 years or below) with the recent onset IDDM (64/113; 57%) compared to patients above the age of 15 years (11/25; 44%). One of 40 (2.5%) Graves' disease patients and five of 204 (2.5%) of NIDDM patients were also positive. IA-2 Abs were not detected in sera from patients with Hashimoto's thyroiditis (n=32), myasthenia gravis (n=20) or systemic lupus erythematosus (n=10). IA-2 Ab measurements based on 125I-labelled IA-2 showed a good correlation with the results of an immunoprecipitation assay based on 35S-labelled IA-2 produced in the in vitro transcription/translation system (r=0.78; n=113; p<0.001). Out of 217 IDDM sera which were tested for IA-2 Abs, 140 (65%) were positive for Abs to glutamic acid decarboxylase (GAD) and 166 (76%) were positive for Abs to IA-2 and/or Abs to GAD. In addition, Abs to IA-2, to GAD and to insulin were analysed in sera from recent onset IDDM patients who had not been treated with insulin (n=117). In all, 76/117 (65%) of these sera were positive for GAD Abs, 66/117 (56%) for IA-2 Abs, 45/117 (38%) for insulin Abs. However, 98/117 (84%) were positive for at least one of the three Abs confirming earlier observations on the complementarity of Ab testing in IDDM. Overall, the IA-2 Ab assay based on 125I-labelled recombinant IA-2 showed good sensitivity, precision and specificity which, combined with an easy and convenient protocol, makes it attractive for routine use.

Adolescent↗

Corporate governance of public health services: lessons from New Zealand for the state sector.

New Zealand public hospitals and related services were grouped into 23 Crown Health Enterprises and registered as companies in 1993. Integral to this change was the introduction of corporate governance. New directors, largely from the business sector, were appointed to govern these organisations as efficient and effective businesses. This article presents the results of a survey of directors of New Zealand publicly-owned health provider organisations. Although directors thought they performed well in business systems development, they acknowledged their shortcomings in meeting government expectations in respect to financial performance and social responsibility. Changes in public health sector provider performance indicators have resulted in a mixed report card for the sector six years after corporate governance was instituted.

Delivery of Health Care↗

Duplex ultrasound screening for deep vein thrombosis in spinal cord injured patients at rehabilitation admission.

OBJECTIVE: To determine the rate of deep vein thrombosis (DVT) newly diagnosed by duplex ultrasound in patients with acute spinal cord injury (SCI) at admission for rehabilitation. DESIGN: Retrospective case-control study. SETTING: Independent specialized spinal cord rehabilitation hospital. PATIENTS: Data were collected from records of 189 SCI patients admitted for rehabilitation over a 1-year period who underwent a duplex scan and were not admitted with a known diagnosis of DVT. MAIN OUTCOME MEASURES: A DVT newly diagnosed by duplex ultrasound at rehabilitation admission. RESULTS: Twenty-two patients (11.6%) had a newly diagnosed DVT at time of admission. Chi-square analysis found no statistically significant relationship between level of injury (tetraplegia vs paraplegia), motor complete (ASIA A and B) versus incomplete status (ASIA C and D), or cause of SCI (traumatic vs nontraumatic injury) in determining a positive or negative duplex result (chi2 = 1.709, p = .191; chi2 = 1.314, p = .252; chi2 = 3.155, p = .076; respectively). Prophylaxis for DVT decreased the risk of developing a DVT: 4.1% of patients administered prophylaxis as compared to 16.4% of patients not given prophylaxis (chi2 = 6.558, p = .01). Only 38.6% of patients transferred to rehabilitation were undergoing DVT prophylaxis. CONCLUSIONS: The prevalence of DVT in acute SCI patients at admission to rehabilitation is significant. A duplex ultrasound is an important noninvasive technique to screen patients with acute and subacute SCI for DVT on admission to the rehabilitation setting regardless of the completeness, level, or cause of the patients' injury.

Adolescent↗

A feasibility study of continuous hyperfractionated accelerated radiotherapy (CHART) and brachytherapy in patients with early oral or oropharyngeal carcinomas.

Overall time is important in the curative treatment of head and neck cancer (Dische, S., Saunders, M.I., Barrett, A., Harvey, A., Gibson, D., Parmar, M., 1997, Radiother. Oncol., 44:123-136). Results are presented on outcome and morbidity in ten patients with head and neck cancer treated with external beam irradiation (CHART protocol) and interstitial implantation, completing treatment in 12 days. Local control and overall survival at 5 years was 67%. Acute and late morbidity was acceptable giving scope for dose escalation.

Adult↗

New labour and the third way in the British National Health Service.

The British Labour Party claims that its policies are based on a "third way," new and distinct from both the old left and the new right. This article critically examines this claim with respect to health policy. After examining the Conservative legacy in the National Health Service and the evolution of Labour's health policy, the author introduces the concept of the "third way" and discusses the extent to which Labour's health policy can be seen in these terms, using the themes of spending, competition, accountability, and public health. There are many differences between the health policies of New and Old Labour, and some differences between those of New Labour and the Conservatives. Indeed, to a large extent Labour's health policy is built on the legacy of the Conservatives and is characterized by evolution. It is difficult to find any "big idea" or coherent philosophy behind the third way. Rather than being a new and distinctive approach rejecting both the old left and the new right, it seems to be a pragmatic pick and mix, attempting to combine the best from the market approach of the Conservatives and the hierarchical approach of Old Labour.

Economic Competition↗

Hormone replacement therapy: determinants of women's decisions.

Hormone replacement therapy: determinants of women's decisions. The purpose of this qualitative study was to explore the decision-making process used by menopausal women initiating or remaining on hormone replacement therapy (HRT), stopping HRT, or never starting HRT. Eight focus groups, composed of women reflecting these categories, were conducted. Four major themes or spheres of influence emerged as important in the women's decision-making process: the woman's internal influence--the interface between her perceptions and feelings including the symptoms of menopause, the benefits realized by HRT usage, and the experiences of negative side effects; interpersonal relationships, including the patient-physician relationship, family, friends and information networks; external influences, such as ageism and sexism; and consequences resulting from whichever treatment decision was chosen. A new concept was elucidated called "weighted influence" to underscore the dynamic interplay among the spheres. As information about HRT continues to grow and change, an understanding and application of these spheres of influence can assist physicians in engaging in a dialogue with their patients that allows individual evaluation and application of this new information.

Adult↗

Experience with dose escalation using CHARTWEL (continuous hyperfractionated accelerated radiotherapy weekend less) in non-small-cell lung cancer.

Results from the multicentre randomized trial of CHART (continuous, hyperfractionated, accelerated radiotherapy) in non-small-cell lung cancer (NSCLC) showed a significant increase in survival (P=0.004) compared with conventional radiotherapy and a therapeutic benefit relative to late radiation-induced morbidity. However, 60% of patients died because of failure to control locoregional disease. These findings have stimulated interest in assessing the feasibility of dose escalation using a modified CHART schedule. Acute and late morbidity with a CHARTWEL (CHART WeekEnd Less) schedule of 54 Gy in 16 days was compared with that observed with 60 Gy in 18 days in patients with locally advanced NSCLC. The incidence and severity of dysphagia and of analgesia were scored using a semiquantitative clinical scale. Late radiation-induced morbidity, namely pulmonary, spinal cord and oesophageal strictures, were monitored using clinical and/or radiological criteria. Acute dysphagia and the analgesia required to control the symptoms were more severe and lasted longer in patients treated with CHARTWEL 60 Gy (P< or = 0.02). However, at 12 weeks, oesophagitis was similar to that seen with 54 Gy and did not lead to consequential damage. Early radiation pneumonitis was not increased but, after 6 months, there was a higher incidence of mild pulmonary toxicity compared with CHARTWEL 54 Gy. No cases of radiation myelitis, oesophageal strictures or of grade 2 or 3 lung morbidity have been encountered. CHARTWEL 60 Gy resulted in an enhancement of oesophagitis and grade 1 lung toxicity compared with CHARTWEL 54 Gy. These were of no clinical significance, but may be important if CHARTWEL is used with concomitant chemotherapy. These results provide a basis for further dose escalation or the introduction of concurrent chemotherapy.

Aged↗

Transsphenoidal management of 28 symptomatic Rathke's cleft cysts, with special reference to visual and hormonal recovery.

OBJECTIVE: This is a retrospective study of a series of 28 Rathke's cleft cysts operated on transsphenoidally that was undertaken for the following reasons: 1) to study the presentation, with particular reference to hormonal and visual disturbances; 2) to study postoperative improvements in endocrine function and vision; 3) to record postoperative complications; and 4) to assess the efficacy of a minor modification of the standard transsphenoidal surgical technique, whereby the cyst is allowed to drain directly into the sphenoid air sinus without fossa floor repair when there is no intraoperative cerebrospinal fluid leak. METHODS: A retrospective study was made of case notes, radiological findings, and operative notes in the series. RESULTS: There were 16 female and 12 male patients, with a mean age of 45 years. Endocrine disturbance was the most common presentation (50%), followed by headaches (32.1%) and visual impairment (14.3%). Neuroophthalmological assessment showed central visual acuity and field deficits in 32.1 and 44.6% of eyes, respectively. Biochemically, 85.7% of patients showed hormonal disturbances. Magnetic resonance imaging was used for 84.7% of cases, and 60.7% of cases showed suprasellar extension. Four magnetic resonance imaging patterns were noted. All cases were operated on transsphenoidally. Postoperative complications included cerebrospinal fluid rhinorrhea (7.1%), diabetes insipidus (3.6%), and meningitis (3.6%). Recovery of visual acuity and field was seen in 66.6 and 68% of eyes, respectively. Postoperative prolactin levels declined to normal or nearly normal values in 62.5% of cases, 20% of cases with low preoperative gonadotrophin levels achieved normal levels, and 15.4% of cases with preoperative pan-hypopituitarism achieved normal serum cortisol levels postoperatively. Within the study period there were no recurrences; although a relatively short time interval is presented for this series, a patient with a similar lesion operated on by the same method 7 years previously remains well, without radiological evidence of recurrence. CONCLUSION: Although comparatively rare and benign lesions, Rathke's cleft cysts are an important cause of hormonal and visual disturbances. Transsphenoidal surgery is safe and efficacious and leads to excellent improvement of function in the majority of cases. The surgical modification described seems safe and satisfactory and is extremely easy to perform.

Adolescent↗

Blunt splenic injury in adults: clinical and CT criteria for management, with emphasis on active extravasation.

PURPOSE: To evaluate and determine the relevance of clinical and computed tomographic (CT) criteria, particularly extravasation, for prediction of clinical outcome in adults with splenic injuries. MATERIALS AND METHODS: Retrospective blinded review was performed of the records of 270 patients with splenic injury during a 5-year period. Of these, 120 died or underwent surgery without CT and 150 underwent dynamic bolus-enhanced CT. Fifty of the latter underwent immediate surgery and 100 initially were treated without surgery, according to CT and clinical criteria: morphologic grade of injury, amount of hemoperitoneum, active extravasation, and injury severity score (a clinical measure of multiorgan trauma). RESULTS: Of the clinical criteria, injury severity score had the best correlation with outcome. Of the CT criteria, active extravasation correlated best with the need for splenic surgery. Of 96 patients selected for nonsurgical treatment and who did not have active extravasation, 83 recovered without surgery or other intervention. Nonsurgical therapy failed in 15 of the 100 patients. The splenic salvage rate was 59.3% overall and was 92% among the 100 patients with initial nonsurgical management. CONCLUSION: Standard clinical criteria allow triage of patients into immediate surgery or initial nonsurgical groups. CT criteria, especially absence of active extravasation, can help predict successful nonsurgical management of splenic injuries.

Abdominal Injuries↗

Effective treatment of chronic plantar fasciitis with dorsiflexion night splints: a crossover prospective randomized outcome study.

Chronic plantar fasciitis frustrates patients and treating physicians. Our hypothesis was that use of a dorsiflexion night splint for 1 month would effectively treat patients with recalcitrant plantar fasciitis. A 6-month randomized crossover study included 37 patients with chronic plantar fasciitis. Patients were treated with dorsiflexion night splints for 1 month. Group A wore splints for the 1st month and group B for the 2nd month. No splints were used in either group for the final 4 months of the study. No other medications, stretching, or strengthening exercises were prescribed. Eighty-eight percent of patients who completed the study improved. Eighty percent of the involved feet improved subjectively. Results of the AOFAS Ankle-Hindfoot Rating System and the Mayo Clinical Scoring System demonstrated significant improvement for both groups during the period of splint wear. Improvements were maintained at study completion. Response to splinting did not correlate with foot type, degree of obesity, or the presence of heel spur on radiographs. We believe dorsiflexion splints provide relief from the symptoms of recalcitrant plantar fasciitis in the majority of patients.

Adult↗

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↗

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↗