Standards of medical care in diabetes.
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Diabetes Mellitus↗
Biomedical subjects
David Power
Publications and source records attributed to David Power.
Obstetric anal sphincter injury: how to avoid, how to repair: a literature review.
Avoiding obstetrical injury to the anal sphincter is the single biggest factor in preventing anal incontinence among women. Any form of instrument delivery has consistently been noted to increase the risk of obstetric anal sphincter injury and altered fecal continence by between 2- and 7-fold. Routine episiotomy is not recommended. Episiotomy use should be restricted to situations where it directly facilitates an urgent delivery. A mediolateral incision, instead of a midline, should be considered for persons at otherwise high risk of obstetric anal sphincter injury. The internal anal sphincter needs to be separately repaired if torn. Women with injuries to the internal anal sphincter or rectal mucosa have a worse prognosis for future continence problems. All women, particularly those with risk factors for injury, should be surveyed for symptoms of anal incontinence at postpartum follow-up.
Anal Canal↗
Designing for e-Health: recurring scenarios in developing grid-based medical imaging systems.
The paper draws on a number of Grid projects, particularly on the experience of NeuroGrid, a UK project in the Neurosciences tasked with developing a Grid-based collaborative research environment to support the sharing of digital images and patient data across multiple distributed sites. It outlines recurrent socio-technical issues, highlighting the challenges of scaling up technological networks in advance of the regulatory networks which normally regulate their use in practice.
Biomedical Research↗
Development of spontaneous multisystem autoimmune disease and hypersensitivity to antibody-induced inflammation in Fcgamma receptor IIa-transgenic mice.
OBJECTIVE: The major human Fc receptor, FcgammaRIIa, is the most widespread activating FcR. Our aim was to determine the role of FcgammaRIIa in a transgenic mouse model of immune complex-mediated autoimmunity and to characterize the development of spontaneous autoimmune disease. METHODS: Arthritis was induced in normal and FcgammaRIIa-transgenic mice by immunization with type II collagen (CII) or by transfer of arthritogenic anti-CII antibodies. Also, mice that spontaneously developed autoimmune disease were assessed by clinical scoring of affected limbs, histology and serology, and measurement of autoantibody titers and cytokine production. RESULTS: FcgammaRIIa-transgenic mice developed collagen-induced arthritis (CIA) more rapidly than did archetypal CIA-sensitive DBA/1 (H-2q) mice, while nontransgenic C57BL/6 (H-2b) mice did not develop CIA when similarly immunized. Passive transfer of a single dose of anti-CII antibody induced a more rapid, severe arthritis in FcgammaRIIa-transgenic mice than in nontransgenic animals. In addition, most immune complex-induced production of tumor necrosis factor alpha by activated macrophages occurred via FcgammaRIIa, not the endogenous mouse FcR. A spontaneous, multisystem autoimmune disease developed in aging (>20 weeks) transgenic mice (n = 25), with a 32% incidence of arthritis, and by 45 weeks, all mice had developed glomerulonephritis and pneumonitis, and most had antihistone antibodies. Elevated IgG2a levels were seen in mice with CIA and in those with spontaneous disease. CONCLUSION: The presence of enhanced passive and induced autoimmunity, as well as the emergence of spontaneous autoimmune disease at 20-45 weeks of age, suggest that FcgammaRIIa is a very important factor in the pathogenesis of autoimmune inflammation and a possible target for therapeutic intervention.
Animals↗
The risks of thin basement membrane nephropathy.
Most individuals with thin basement membrane nephropathy (TBMN) have an excellent prognosis. For these patients, the only hazards are the anxiety related to misconceptions about the diagnosis and the inconvenience, expense, and wastefulness of unnecessary investigations. However, there also are specific genetic implications for individuals with TBMN because, on average, half their offspring inherit the causative mutations and most of these have hematuria. In addition, despite the generally excellent outcome, some individuals with TBMN develop hypertension, proteinuria, or renal impairment. In some cases, renal failure is caused by apparently progressive but otherwise uncomplicated TBMN, and in others it results from a secondary or coincidental glomerular or tubulointerstitial renal lesion. In particular, TBMN appears to predispose to immunoglobulin (Ig)A glomerulonephritis, and the outcome for these patients is worse than for those with TBMN alone. The risks for patients with TBMN in relation to pregnancy and transplantation have not been well-studied but are described elsewhere in this issue.
Diagnostic Errors↗
Velopharyngeal port status during classical singing.
PURPOSE: This investigation was undertaken to examine the status of the velopharyngeal (VP) port during classical singing. METHOD: Using aeromechanical instrumentation, nasal airflow (mL/s), oral pressure (cm H2O), and VP orifice area estimates (cm2) were studied in 10 classically trained sopranos during singing and speaking. Each participant sang and spoke 3 nonsense words-/hampa/, /himpi/, and /humpu/-at 3 loudness levels (loud vs. comfortable vs. soft) and 3 pitches (high vs. comfortable vs. low), using a within-subject experimental design including all possible combinations. RESULTS: In general, nasal airflow, oral pressure, and VP area estimates were significantly greater for singing as compared to speech, and nasal airflow was observed during non-nasal sounds in all participants. Anticipatory nasal airflow was observed in 9 of 10 participants for singing and speaking and was significantly greater during the first vowel in /hampa/ versus /himpi/ and /humpu/. The effect of vowel height on nasal airflow was also significantly influenced by loudness and pitch. CONCLUSIONS: The results from this investigation indicate that at least some trained singers experience regular VP opening during classical singing. Vowel height seems to influence this effect. Future research should consider the effects of voice type, gender, experience level, performance ability, and singing style on VP valving in singers.
Adult↗
The increased incidence of pure red cell aplasia with an Eprex formulation in uncoated rubber stopper syringes.
BACKGROUND: The incidence of pure red cell aplasia (PRCA) in chronic kidney disease patients treated with epoetins increased substantially in 1998, was shown to be antibody mediated, and was associated predominantly with subcutaneous administration of Eprex. A technical investigation identified organic compounds leached from uncoated rubber stoppers in prefilled syringes containing polysorbate 80 as the most probable cause of the increased immunogenicity. METHODS: This study investigated whether the incidence of PRCA was higher for exposure to the product form containing leachates than for leachate-free product forms. Antibody-mediated PRCA cases were classified according to indication, product form, and route of administration. Exposure estimates were obtained by country, indication, route of administration, and product form. RESULTS: For 2001 to 2003, the PRCA incidence rate for patients with subcutaneous exposure to Eprex in prefilled syringes with polysorbate 80 and uncoated rubber stoppers (leachates present) was 4.61/10,000 patient years (95% CI 3.88-5.43) versus 0.26/10,000 patient years (95% CI 0.007-1.44) for syringes with coated stoppers (leachates absent). The rate difference was 4.35/10,000 patient years (95% CI 3.44-5.26; P < 0.0001); the rate ratio was 17 (95% CI 3.14-707). A substantial rate difference remained in sensitivity analyses that adjusted for exposure to multiple product forms. CONCLUSION: The epidemiologic data, together with the chemical and immunologic data, support the hypothesis that leachates from uncoated rubber syringe stoppers caused the increased incidence of PRCA associated with Eprex. Currently, all Eprex prefilled syringes contain fluoro-resin coated stoppers, which has contributed to decreased incidence of PRCA with continued surveillance.
Chemistry, Pharmaceutical↗
Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement.
The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function. The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%. The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to "automatically" generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m", rather than as a precise figure.
Journal Article↗
The detection of anti-erythropoietin antibodies in human serum and plasma. Part I. Validation of the protocol for a radioimmunoprecipitation assay.
Rare cases of unexplained sudden severe anemia or red cell aplasia and resistance to recombinant human erythropoietin (rHuEPO) in patients with chronic renal failure (CRF) have been attributed to the development of anti-EPO antibodies. The development and validation of a radioimmunoprecipitation (RIP) assay to detect human anti-EPO antibodies in serum or plasma has been hampered by the lack of purified antibody to fully characterize and validate the assay. We have prepared an affinity-purified human antibody to EPO and used the antibody to characterize and validate a sensitive and reproducible RIP assay that can qualitatively measure anti-EPO antibody in serum or plasma samples. The lower limit of detection of the assay is 8 ng/ml of purified antibody. The threshold for detecting antibody is > or =0.9% cpm bound. The precision of the assay using purified antibody standards ranges from 5.8% to 15.3% and the precision of the assay using dilutions of the positive control ranges from 15.9% to 18.7%. EPO in the samples did not interfere with detection of the anti-EPO antibody except at high concentrations.
Antibodies↗
Granulocyte function in grancalcin-deficient mice.
Grancalcin, one of the penta-EF-hand Ca(2+) binding proteins, is expressed at high levels in polymorphonuclear granulocytes (neutrophils). EF-hand proteins are implicated in the regulation of diverse processes including cell migration, apoptosis, and mobilization of neutrophil effector functions. To determine the role of grancalcin in vivo, we inactivated the gene encoding grancalcin (Gca) in embryonic stem cells and generated grancalcin-deficient mice. Homozygous Gca mutants appeared healthy and reproduced normally. Leukocyte recruitment into the peritoneal cavity upon induction of inflammation was not significantly affected by the absence of grancalcin. The mutants also resisted systemic fungal infection similarly to wild-type mice, and in vitro killing of Staphylococcus aureus by inflammatory cells was not significantly impaired. While marginally increased survival rates of mutants faced with endotoxic shock may indicate a contribution of grancalcin to immunopathogenesis, it is not essential for vital leukocyte effector functions required to control microbial infections.
Animals↗
Unrecognized anemia in patients with diabetes: a cross-sectional survey.
OBJECTIVE: Anemia is common in diabetes, potentially contributing to the pathogenesis of diabetes complications. This study aims to establish the prevalence and independent predictors of anemia in a cross-sectional survey of 820 patients with diabetes in long-term follow-up in a single clinic. RESEARCH DESIGN AND METHODS: A full blood count was obtained in addition to routine blood and urine test results for all patients over a 2-year period to encompass all patterns of review. Predictors of the most recent Hb concentration and anemia were identified using multiple and logistic regression analysis. RESULTS: A total of 190 patients (23%) had unrecognized anemia (Hb <12 g/dl for women and <13 g/dl for men). This prevalence is two to three times higher than for patients with comparable renal impairment and iron stores in the general population. Independent predictors for Hb were transferrin saturation, glomerular filtration rate (GFR), sex, albumin excretion rate, and HbA(1c) level (all P < 0.0001). Microalbuminuric patients were >2 times (odds ratio [OR] 2.3) and macroalbuminuric patients >10 times (OR 10.1) as likely to have anemia than normoalbuminuric patients with preserved renal function (GFR >80 ml/min). CONCLUSIONS: Anemia is a common accompaniment to diabetes, particularly in those with albuminuria or reduced renal function. Additional factors present in diabetes may contribute to the development of increased risk for anemia in patients with diabetes.
Albuminuria↗
Ym1 is a neutrophil granule protein that crystallizes in p47phox-deficient mice.
Crystals were discovered within the aged lung and at sites of chronic inflammation in a mouse model of chronic granulomatous disease. Following re-crystallization at neutral pH, the crystals were identified as the chitinase-like protein Ym1, expressed in organs of the lymphoreticular system, the lung, and distal stomach. Ym1 was shown to be a neutrophil granule protein and to have weak beta-N-acetylglucosaminidase activity, indicating that it might contribute to the digestion of glycosaminoglycans. Crystal formation is likely to be a function of excess neutrophil turnover at sites of inflammation in the chronic granulomatous disease mouse. Failure to remove subcutaneous Ym1 crystals injected into knockout mice indicates that a failure of digestion may also contribute to crystallization.
Animals↗