Metabolic myopathy presenting with polyarteritis nodosa: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, we describe for the first time a patient in whom an unusual metabolic myopathy was identified after failure to respond to curative therapy for a systemic vasculitis, polyarteritis nodosa. We hope this report will heighten awareness of common metabolic myopathies that may present later in life. It also speculates on the potential relationship between metabolic myopathy and systemic vasculitis.</p> <p>Case presentation</p> <p>A 78-year-old African-American woman with a two-year history of progressive fatigue and exercise intolerance presented to our facility with new skin lesions and profound muscle weakness. Skin and muscle biopsies demonstrated a medium-sized artery vasculitis consistent with polyarteritis nodosa. Biochemical studies of the muscle revealed diminished cytochrome C oxidase activity (0.78 μmol/minute/g tissue; normal range 1.03 to 3.83 μmol/minute/g tissue), elevated acid maltase activity (23.39 μmol/minute/g tissue; normal range 1.74 to 9.98 μmol/minute/g tissue) and elevated neutral maltase activity (35.89 μmol/minute/g tissue; normal range 4.35 to 16.03 μmol/minute/g tissue). Treatment for polyarteritis nodosa with prednisone and cyclophosphamide resulted in minimal symptomatic improvement. Additional management with a diet low in complex carbohydrates and ubiquinone, creatine, carnitine, folic acid, α-lipoic acid and ribose resulted in dramatic clinical improvement.</p> <p>Conclusions</p> <p>Our patient's initial symptoms of fatigue, exercise intolerance and progressive weakness were likely related to her complex metabolic myopathy involving both the mitochondrial respiratory chain and glycogen storage pathways. Management of our patient required treatment of both the polyarteritis nodosa as well as metabolic myopathy. Metabolic myopathies are common and should be considered in any patient with exercise intolerance. Metabolic myopathies may complicate the management of various disease states.</p

Quantifying geocode location error using GIS methods

BACKGROUND: The Metropolitan Atlanta Congenital Defects Program (MACDP) collects maternal address information at the time of delivery for infants and fetuses with birth defects. These addresses have been geocoded by two independent agencies: (1) the Georgia Division of Public Health Office of Health Information and Policy (OHIP) and (2) a commercial vendor. Geographic information system (GIS) methods were used to quantify uncertainty in the two sets of geocodes using orthoimagery and tax parcel datasets. METHODS: We sampled 599 infants and fetuses with birth defects delivered during 1994–2002 with maternal residence in either Fulton or Gwinnett County. Tax parcel datasets were obtained from the tax assessor's offices of Fulton and Gwinnett County. High-resolution orthoimagery for these counties was acquired from the U.S. Geological Survey. For each of the 599 addresses we attempted to locate the tax parcel corresponding to the maternal address. If the tax parcel was identified the distance and the angle between the geocode and the residence were calculated. We used simulated data to characterize the impact of geocode location error. In each county 5,000 geocodes were generated and assigned their corresponding Census 2000 tract. Each geocode was then displaced at a random angle by a random distance drawn from the distribution of observed geocode location errors. The census tract of the displaced geocode was determined. We repeated this process 5,000 times and report the percentage of geocodes that resolved into incorrect census tracts. RESULTS: Median location error was less than 100 meters for both OHIP and commercial vendor geocodes; the distribution of angles appeared uniform. Median location error was approximately 35% larger in Gwinnett (a suburban county) relative to Fulton (a county with urban and suburban areas). Location error occasionally caused the simulated geocodes to be displaced into incorrect census tracts; the median percentage of geocodes resolving into incorrect census tracts ranged between 4.5% and 5.3%, depending upon the county and geocoding agency. CONCLUSION: Geocode location uncertainty can be estimated using tax parcel databases in a GIS. This approach is a viable alternative to global positioning system field validation of geocodes

Sanitation and Health

As one article in a four-part PLoS Medicine series on water and sanitation, David Trouba and colleagues discuss the importance of improved sanitation to health and the role that the health sector can play in its advocacy

Gap junctions in olfactory neurons modulate olfactory sensitivity

<p>Abstract</p> <p>Background</p> <p>One of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium. On the basis that mature ORNs express multiple connexins, I postulated that gap junctional communication modulates olfactory responses in the periphery and that disruption of gap junctions in ORNs reduces olfactory sensitivity. The data collected from characterizing connexin 43 (Cx43) dominant negative transgenic mice OlfDNCX, and from calcium imaging of wild type mice (WT) support my hypothesis.</p> <p>Results</p> <p>I generated OlfDNCX mice that express a dominant negative Cx43 protein, Cx43/β-gal, in mature ORNs to inactivate gap junctions and hemichannels composed of Cx43 or other structurally related connexins. Characterization of OlfDNCX revealed that Cx43/β-gal was exclusively expressed in areas where mature ORNs resided. Real time quantitative PCR indicated that cellular machineries of OlfDNCX were normal in comparison to WT. Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT. Octaldehyde-elicited glomerular activity in the olfactory bulb, measured according to odor-elicited <it>c-fos </it>mRNA upregulation in juxtaglomerular cells, was confined to smaller areas of the glomerular layer in OlfDNCX compared to WT. In WT mice, octaldehyde sensitive neurons exhibited reduced response magnitudes after application of gap junction uncoupling reagents and the effects were specific to subsets of neurons.</p> <p>Conclusions</p> <p>My study has demonstrated that altered assembly of Cx43 or structurally related connexins in ORNs modulates olfactory responses and changes olfactory activation maps in the olfactory bulb. Furthermore, pharmacologically uncoupling of gap junctions reduces olfactory activity in subsets of ORNs. These data suggest that gap junctional communication or hemichannel activity plays a critical role in maintaining olfactory sensitivity and odor perception.</p

The survival benefit of liver transplantation in hepatocellular carcinoma patients

Abstract Background There are no studies evaluating the survival benefit of liver transplantation over alternative therapies for patients with hepatocellular carcinoma. Methods The short- to mid-term survival benefit (study group = 135 aggressively treated patients with hepatocellular carcinoma, 52% beyond Milan criteria at pathology) was calculated by comparing the mortality rates of liver transplantation vs alternative therapies patients. A Markov prediction model was then created to estimate the long-term survival benefit of liver transplantation (gain in life expectancy) over alternative therapies. The long-term survival rates in the liver transplantation group were calculated using the Metroticket website calculator (http://89.96.76.14/metroticket/calculator/). Results The short- to mid-term analysis indicated that liver transplantation afforded no significant survival benefit in the group of patients with hepatoma as a whole (hazard ratio = 1.229, 95% confidence interval 0.544\u20132.773, p = .6200). The benefit was concentrated in patients with a poor initial response to alternative therapies (hazard ratio = 3.137, 95% confidence interval 1.428\u20136.891, p = .0044). In the long-term analysis, the gain in life expectancy of liver transplantation vs alternative therapies was 6.115 years (base-case analysis) and the main determinants of gain in life expectancy were the 5-year survival prospects after alternative therapies and the patient's age. Conclusions The survival benefit of liver transplantation for patients with hepatocellular carcinoma is strongly related to the patient's age and the effectiveness of available alternative therapies

Estimation of the harm to the waiting list as a crucial factor in the selection of patients with hepatocellular carcinoma for liver transplantation.

BACKGROUND: Long-term survival rates after orthotopic liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) of any size and number may now be predicted using the Metroticket calculator. The aim of this study was to evaluate the minimum post-OLT survival threshold that would justify the selection of a patient with HCC for OLT. METHODS: We used a Markov model, recently developed at the University of Michigan, which assumes that a patient with HCC should undergo OLT if his or her transplant benefit is greater than the cumulative harm to the rest of the waiting list (WL). In the base case, we considered a patient with a low survival perspective without OLT (5-year survival rate, 10%). The data sources to construct and validate the model were as follows: the Organ Procurement and Transplantation Network report, and our prospective database. RESULTS: Our center was generally characterized by lower WL mortalities, although there were lower transplant probabilities for both HCC and non-HCC patients than the average US center. The proportion of HCC patients on the WL was higher in Padua (25%) than in the United States (10%). The calculated harm to the WL was 434 quality-adjusted days of life in Padua, and 957 in the United States (P < .01). The OLT benefit outweighed the harm to the WL when the 5-year post-OLT survival rate was higher than 30% in Padua, and 61% in the United States. CONCLUSIONS: In a decision model including the concepts of transplantation benefit and harm to the WL, the minimum 5-year post-OLT survival threshold justifying the selection of a patient with HCC for OLT in Padua was 30%